Contents PAGEREF _Toc508531687 h 283.1. STUDY DESIGN

Contents TOC o “1-3” h z u LIST OF FIGURES PAGEREF _Toc508531671 h iiiLIST OF TABLES PAGEREF _Toc508531672 h ivLIST OF ABBREVIATIONS PAGEREF _Toc508531673 h vABSTRACT PAGEREF _Toc508531674 h viiiCHAPTER 1: INTRODUCTION PAGEREF _Toc508531675 h 11.1. BACKGROUND PAGEREF _Toc508531676 h 11.2.

RESEARCH QUESTION; PAGEREF _Toc508531677 h 21.3. HYPOTHESIS; PAGEREF _Toc508531678 h 21.4.

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OBJECTIVES; PAGEREF _Toc508531679 h 21.4.1. Overall research aim PAGEREF _Toc508531680 h 21.4.2.

Specific objectives PAGEREF _Toc508531681 h 2CHAPTER 2: LITERATURE REVIEW PAGEREF _Toc508531682 h 52.1. HYPERTROPHIC CARDIOMYOPATHY (HCM) PAGEREF _Toc508531683 h 52.

2. OXIDATIVE STRESS PAGEREF _Toc508531684 h 102.2.1. OXIDATIVE STRESS AND HCM PAGEREF _Toc508531685 h 152.2.2.

ROS, SIGNALING PATHWAYS AND HCM PAGEREF _Toc508531686 h 17CHAPTER 3: METHODOLOGY. PAGEREF _Toc508531687 h 283.1. STUDY DESIGN PAGEREF _Toc508531688 h 283.1.

1. Type and site of the study PAGEREF _Toc508531689 h 283.1.2.

Study population PAGEREF _Toc508531690 h 283.2. PATIENT’S HISTORY; PAGEREF _Toc508531691 h 283.2.1. Patient 1; PAGEREF _Toc508531692 h 293.2.2.

Patient 2; PAGEREF _Toc508531693 h 303.2.3.

Patient 3; PAGEREF _Toc508531694 h 323.3. RESEARCH CONCEPT PAGEREF _Toc508531695 h 343.4. MATERIALS PAGEREF _Toc508531696 h 353.5. METHODS PAGEREF _Toc508531697 h 363.

5.1. Making PB solution PAGEREF _Toc508531698 h 363.5.

2. Making 30% sucrose solution PAGEREF _Toc508531699 h 363.5.3. Making 20% sucrose solution PAGEREF _Toc508531700 h 363.5.

4. Making the store solution PAGEREF _Toc508531701 h 363.5.5. Making a working solution PAGEREF _Toc508531702 h 363.5.6.

Fixing and slicing the heart samples PAGEREF _Toc508531703 h 373.5.7. Staining of the heart samples and ROS visualization. PAGEREF _Toc508531704 h 373.

5.8. Analysis PAGEREF _Toc508531705 h 373.

6. ETHICAL CONSIDERATION PAGEREF _Toc508531706 h 38CHAPTER 4: RESULTS PAGEREF _Toc508531707 h 394.1. Microscopy images and Image J analysis PAGEREF _Toc508531708 h 394.2. SPSS statistical analysis. PAGEREF _Toc508531709 h 414.2.

1. Analysis of the First heart. PAGEREF _Toc508531710 h 424.

2.2. Analysis of the second heart. PAGEREF _Toc508531711 h 444.2.3.

Analysis of the Third heart Sample. PAGEREF _Toc508531712 h 47CHAPTER 5: DISCUSSION PAGEREF _Toc508531713 h 525.1. LIMITATION AND STREGHTH OF THE STUDY PAGEREF _Toc508531714 h 54CHAPTER 6: CONCLUSION PAGEREF _Toc508531715 h 55CHAPTER 7: REFERENCES.

PAGEREF _Toc508531716 h 56LIST OF FIGURES TOC h z c “Figure” Figure 1. Histologic subtypes of the heart samples. PAGEREF _Toc508527979 h 4Figure 2. Four steps reduction of oxygen to form water.

PAGEREF _Toc508527980 h 9Figure 3. Fenton reaction. PAGEREF _Toc508527981 h 10Figure 4. The MAPK signaling pathway, PAGEREF _Toc508527982 h 16Figure 5. PI3K/Akt/mTOR signaling cascade PAGEREF _Toc508527983 h 19Figure 6. Calcineurin/ NF-AT signaling pathway PAGEREF _Toc508527984 h 22Figure 7.

NF-KB signaling pathway activation. PAGEREF _Toc508527985 h 24Figure 8. Fluorescent microscopy images showing ROS in different heart chambers with HCM.

PAGEREF _Toc508527986 h 38Figure 9. Image j analysis of the above fluorescent images from figure 8. PAGEREF _Toc508527987 h 39Figure 10. Bar chart showing the mean amount of reactive oxygen species in the heart chambers of the first patient’s heart. PAGEREF _Toc508527988 h 40Figure 11.Bar chart showing the mean value of ROS in different chambers of the second heart. PAGEREF _Toc508527989 h 43Figure 12.

Bar chart showing mean value of ROS in different chambers of the third heart. PAGEREF _Toc508527990 h 46Figure 13. Chamber wise comparison of mean ROS in the three hearts.

PAGEREF _Toc508527991 h 49LIST OF TABLES TOC h z c “Table” Table 1: Description statistics of ROS the first heart. PAGEREF _Toc508531187 h 42Table 2: ANOVA of ROS in the first heart PAGEREF _Toc508531188 h 43Table 3: Multiple comparison of ROS in the first heart PAGEREF _Toc508531189 h 43Table 4: Descriptive statistic of ROS in the second heart PAGEREF _Toc508531190 h 45Table 5: ANOVA of ROS in the second heart PAGEREF _Toc508531191 h 46Table 6: Multiple comparison in the mean ROS in the second heart PAGEREF _Toc508531192 h 46Table 7: Descriptive statistic of ROS in the third heart PAGEREF _Toc508531193 h 48Table 8: ANOVA of ROS in the third heart PAGEREF _Toc508531194 h 49Table 9: Multiple comparison of mean ROS from the third heart PAGEREF _Toc508531195 h 49LIST OF ABBREVIATIONS HCM Hypertrophic cardiomyopathyROS Reactive oxygen speciesDHE DihydroethidiumKCNQ4 Potassium voltage gated channel subfamily KQT member 4SCD Sudden cardiac deathHMG-COA 3- Hydroxy-3- Methyl- Glutaryl- Co enzyme ANAC N- Acetyl cysteine?- MyHCBeta myocin heavy chainMyBPMyocin binding proteincTnTCardiac troponin TAF Atrial fibrillationH&E Hematoxylin and EosinACE Angiotensin converting enzyme ICD Implantable Cardiovertor DefibrillatorAIDC Automated Implantable Cardiovertor DefibrillatorLVAD Left Ventricular Assisted DeviceO-2 Superoxide anionsH2O2 Hydrogen peroxideHO Hydroxyl radicals NO Nitric OxideONOO- Peroxy Nitrite Anions ATP Adenosine TriphosphateNADPH Nicotinamide Adenine Dinucleotide PhosphateNADH Nicotinamide Adenine DinucleotideHOCL Hypochlorous acidFe IronCu Copper AP-1 Activator protein 1NF-kBNuclear Factor Kappa – light – chain enhancer of activated B cellsDNA Deoxyribonucleic acidALCAT1 Lysocardiolipin Acyltransferase 1MAPK Mitogen activated protein kinasePI3K-AKT Phosphatidylinositol 3- kinase- protein kinase BNF-AT Nuclear factor of activated T cellCa2+ Calcium ionsNa+ Sodium ionsFADH2 Flavine adenine dinuceotideH+ Hydrogen ionsmTORMammalian target of rapamycinRAF Rapidly accelerated fibrosarcomaERK Extracellular signal regulated kinasesGDP Guanosine 5′- DiphosphateGTP Guanosine 5′- TriphosphateGAPs GTPase activating proteins JNKs C- Jun N- terminal kinasesUV light Ultraviolet lightTRX1 Theoredoxin 1RTK Receptor tyrosine kinaseIRS1 Insulin receptor substrate 1PIP2 Phosphatidylinositol 4,5- BiphoshatePIP3 Phosphatidylinositol 3,4,5- TriphosphateMRNA Messenger ribonucleic acidPtPn1 Tyrosine protein phosphatase non- receptor type 1NSML Noonan syndrome with multiple lentiginesPTEN Phosphatase and tensin homologNIK NF-kB inducing kinaseTRAF3 Tumor necrosis factor – receptor associated factor 3TRAF2 Tumor necrosis factor – receptor associated factor 2CiAPCellular inhibitor of apoptosisIL Interleukin PDTC Pyrrolidine dithiocarbamateBP Blood pressure PR Pulse rateRR Respiratory rateEF Ejection fractionKG Kilogram HBSS Hank’s balanced salt solutionDMSO Anhydrous dimethyl sulfoxideOCT Optimal cutting temperature NYHA New york heart associationTNNI3 Troponin I, cardiac musclePB solution Phosphate buffer solutionSPSS Statistical package for the social sciences ANOVA Analysis of varianceHNE 4- hydroxyl- 2- nonenolFK506 Tacrolimus AKAP 79 A- kinase anchor protein 79PICOT PKC interacting cousin of thioredoxin ABSTRACTBackground: Hypertrophic cardiomyopathy (HCM) is a genetic heart disease with an autosomal dominant mode of inheritance but can occur sporadically. It mostly occurs due to mutation in the sarcomeric gene proteins. Despite its genetic factor, only few patients have phenotypic expression of the disease and some do not. Increase in oxidative stress in the heart muscles plays a significant role in the phenotypic expression of the disease.

High amount of reactive oxygen species (ROS) plays a significant role in the myocardial hypertrophy, myocardial fibrosis, necrosis of the muscles, apoptosis and have been implicated in heart failure as per many studies that have already been done, features which are also present in HCM patients. Furthermore, oxidative stress (high ROS), plays a significant role in activating important cell signaling pathways which are also activated in patients with HCM. So far the management of HCM is based on relieving symptoms but blocking the oxidative stress could provide a possible means of reversing and even blocking the phenotypic expression of the disease. Few researches have proved the increase in oxidative stress in the HCM animal models but very few if any have proved in humans.

Objective: To observe and prove the increase in the oxidative stress in the human hearts with hypertrophic cardiomyopathy as compared to the normal hearts.Method: An experimental study was done on four human hearts; three were diseased hearts from patients with hypertrophic cardiomyopathy after heart transplant and one from a normal heart chamber. Amount of ROS was tested in the heart tissues using Dihydroethidium (DHE) staining. Each chamber in each heart was tested separately in order to determine the chamber with the highest amount of ROS and hence a highly destructed chamber. Results: The mean amount of ROS was significantly high in the hearts with hypertrophic cardiomyopathy as compared to the normal heart with the p value of ;0.0001 in most of the chambers. In chamber wise comparison, the left ventricle had significantly highest amount of ROS in all the hearts followed by the right ventricle then the right atrium and lastly the normal heart. Heart from the third patient with systolic dysfunction had equal increase in oxidative stress as the other two hearts with Diastolic dysfunction.

Conclusion; there is a significant increase in the reactive oxygen species in the hearts of patients with hypertrophic cardiomyopathy.Key words: Hypertrophic cardiomyopathy, oxidative stress.CHAPTER 1: INTRODUCTION1.1.

BACKGROUNDHypertrophic cardiomyopathy (HCM) is a genetic heart disease with an autosomal dominant mode of inheritance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 1, 2.

It is the most common cause of sudden cardiac death in 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ADDIN EN.CITE <EndNote><Cite><Author>Marian</Author><Year>2001</Year><RecNum>4</RecNum><DisplayText>[3-5]</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1516105389">4</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Marian, A. J.</author><author>Roberts, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. amarian@bcm.tmc.edu</auth-address><titles><title>The molecular genetic basis for hypertrophic cardiomyopathy</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>655-70</pages><volume>33</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/metabolism/pathology</keyword><keyword>Disease Models, Animal</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Phenotype</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2828 (Print)&#xD;0022-2828 (Linking)</isbn><accession-num>11273720</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11273720</url></related-urls></urls><custom2>2901497</custom2><electronic-resource-num>10.1006/jmcc.2001.1340</electronic-resource-num></record></Cite><Cite><Author>Fernlund</Author><Year>2017</Year><RecNum>179</RecNum><record><rec-number>179</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1492420224">179</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fernlund, E.</author><author>Gyllenhammar, T.</author><author>Jablonowski, R.</author><author>Carlsson, M.</author><author>Larsson, A.</author><author>Arnlov, J.</author><author>Liuba, P.</author></authors></contributors><auth-address>Pediatric Heart Center, Skane University Hospital, Lund University, Lund, Sweden. eva.fernlund@gmail.com.&#xD;Department of Paediatrics, Linkoping University Hospital, Linkoping University, Linkoping, Sweden. eva.fernlund@gmail.com.&#xD;Department of Clinical Sciences, Lund University Hospital, Lund University, Lund, Sweden.&#xD;Department of Medical Sciences, Uppsala University, Uppsala, Sweden.&#xD;Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.&#xD;Department of Neurobiology, Division of Family Medicine and Primary Care, Care Science and Society, Karolinska Institutet, Huddinge, Sweden.&#xD;Pediatric Heart Center, Skane University Hospital, Lund University, Lund, Sweden.</auth-address><titles><title>Serum Biomarkers of Myocardial Remodeling and Coronary Dysfunction in Early Stages of Hypertrophic Cardiomyopathy in the Young</title><secondary-title>Pediatr Cardiol</secondary-title><alt-title>Pediatric cardiology</alt-title></titles><periodical><full-title>Pediatr Cardiol</full-title><abbr-1>Pediatric cardiology</abbr-1></periodical><alt-periodical><full-title>Pediatr Cardiol</full-title><abbr-1>Pediatric cardiology</abbr-1></alt-periodical><pages>853-863</pages><volume>38</volume><number>4</number><dates><year>2017</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1432-1971 (Electronic)&#xD;0172-0643 (Linking)</isbn><accession-num>28361263</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28361263</url></related-urls></urls><electronic-resource-num>10.1007/s00246-017-1593-x</electronic-resource-num></record></Cite><Cite><Author>Maron</Author><Year>2006</Year><RecNum>12</RecNum><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1514978881">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Maron, B. J.</author><author>Pelliccia, A.</author></authors></contributors><auth-address>The Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, 920 East 28th St, Suite 60, Minneapolis, MN 55407, USA. hcm.maron@mhif.org</auth-address><titles><title>The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>1633-44</pages><volume>114</volume><number>15</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Arrhythmias, Cardiac/complications/pathology/physiopathology</keyword><keyword>Athletic Injuries/*etiology/physiopathology</keyword><keyword>Cardiomegaly/complications/pathology/physiopathology</keyword><keyword>Death, Sudden, Cardiac/*etiology/pathology</keyword><keyword>Echocardiography</keyword><keyword>Electrocardiography</keyword><keyword>Exercise/physiology</keyword><keyword>Heart/*physiology/physiopathology</keyword><keyword>Humans</keyword><keyword>Myocardium/pathology</keyword><keyword>Risk Factors</keyword><keyword>Sports/*physiology</keyword><keyword>Sports Medicine/legislation &amp; jurisprudence</keyword><keyword>Ventricular Remodeling/*physiology</keyword></keywords><dates><year>2006</year><pub-dates><date>Oct 10</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>17030703</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17030703</url></related-urls></urls><electronic-resource-num>10.1161/CIRCULATIONAHA.106.613562</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 3-5 with the prevalence of 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ADDIN EN.CITE.DATA 6, 7 .It is caused by mutation in the contractile sarcomeric protein gene though mutation in non-sarcomeric protein genes like potassium voltage gated channels (KCNQ4) have also been reported.

The management of HCM being either surgical like septal 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 ADDIN EN.CITE <EndNote><Cite><Author>Maron</Author><Year>2004</Year><RecNum>9</RecNum><DisplayText>[8-10]</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="0edasxaear9z04ewsayv2frgedxaz9dep90z" timestamp="1512192497">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Maron, B. J.</author><author>Dearani, J. A.</author><author>Ommen, S. R.</author><author>Maron, M. S.</author><author>Schaff, H. V.</author><author>Gersh, B. J.</author><author>Nishimura, R. A.</author></authors></contributors><auth-address>Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota 55407, USA. hcm.maron@mhif.org &lt;hcm.maron@mhif.org&gt;</auth-address><titles><title>The case for surgery in obstructive hypertrophic cardiomyopathy</title><secondary-title>J Am Coll Cardiol</secondary-title><alt-title>Journal of the American College of Cardiology</alt-title></titles><periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></periodical><alt-periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></alt-periodical><pages>2044-53</pages><volume>44</volume><number>10</number><keywords><keyword>Cardiomyopathy, Hypertrophic/*surgery</keyword><keyword>Decision Trees</keyword><keyword>Humans</keyword><keyword>Ventricular Outflow Obstruction/*surgery</keyword></keywords><dates><year>2004</year><pub-dates><date>Nov 16</date></pub-dates></dates><isbn>0735-1097 (Print)&#xD;0735-1097 (Linking)</isbn><accession-num>15542290</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15542290</url></related-urls></urls><electronic-resource-num>10.1016/j.jacc.2004.04.063</electronic-resource-num></record></Cite><Cite><Author>Ommen</Author><Year>2005</Year><RecNum>7</RecNum><record><rec-number>7</rec-number><foreign-keys><key app="EN" db-id="0edasxaear9z04ewsayv2frgedxaz9dep90z" timestamp="1512191994">7</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ommen, S. R.</author><author>Maron, B. J.</author><author>Olivotto, I.</author><author>Maron, M. S.</author><author>Cecchi, F.</author><author>Betocchi, S.</author><author>Gersh, B. J.</author><author>Ackerman, M. J.</author><author>McCully, R. B.</author><author>Dearani, J. A.</author><author>Schaff, H. V.</author><author>Danielson, G. K.</author><author>Tajik, A. J.</author><author>Nishimura, R. A.</author></authors></contributors><auth-address>Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. ommen.steve@mayo.edu</auth-address><titles><title>Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy</title><secondary-title>J Am Coll Cardiol</secondary-title><alt-title>Journal of the American College of Cardiology</alt-title></titles><periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></periodical><alt-periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></alt-periodical><pages>470-6</pages><volume>46</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Aged</keyword><keyword>Analysis of Variance</keyword><keyword>Cardiac Surgical Procedures/methods</keyword><keyword>Cardiomyopathy, Hypertrophic/diagnostic imaging/*mortality/*surgery</keyword><keyword>*Cause of Death</keyword><keyword>Cohort Studies</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Heart Septum/*surgery</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Probability</keyword><keyword>Retrospective Studies</keyword><keyword>Risk Assessment</keyword><keyword>Severity of Illness Index</keyword><keyword>Sex Factors</keyword><keyword>Survival Analysis</keyword><keyword>Time</keyword><keyword>Treatment Outcome</keyword><keyword>Ultrasonography</keyword><keyword>Ventricular Outflow Obstruction/diagnostic imaging/*mortality/*surgery</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug 2</date></pub-dates></dates><isbn>0735-1097 (Print)&#xD;0735-1097 (Linking)</isbn><accession-num>16053960</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16053960</url></related-urls></urls><electronic-resource-num>10.1016/j.jacc.2005.02.090</electronic-resource-num></record></Cite><Cite><Author>Rastegar</Author><Year>2017</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="0edasxaear9z04ewsayv2frgedxaz9dep90z" timestamp="1512192267">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rastegar, H.</author><author>Boll, G.</author><author>Rowin, E. J.</author><author>Dolan, N.</author><author>Carroll, C.</author><author>Udelson, J. E.</author><author>Wang, W.</author><author>Carpino, P.</author><author>Maron, B. J.</author><author>Maron, M. S.</author><author>Chen, F. Y.</author></authors></contributors><auth-address>Hypertrophic Cardiomyopathy Center and Research Institute, Divisions of Cardiology and Cardiothoracic Surgery, Tufts Medical Center, Boston, MA, USA.</auth-address><titles><title>Results of surgical septal myectomy for obstructive hypertrophic cardiomyopathy: the Tufts experience</title><secondary-title>Ann Cardiothorac Surg</secondary-title><alt-title>Annals of cardiothoracic surgery</alt-title></titles><periodical><full-title>Ann Cardiothorac Surg</full-title><abbr-1>Annals of cardiothoracic surgery</abbr-1></periodical><alt-periodical><full-title>Ann Cardiothorac Surg</full-title><abbr-1>Annals of cardiothoracic surgery</abbr-1></alt-periodical><pages>353-363</pages><volume>6</volume><number>4</number><dates><year>2017</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>2225-319X (Print)&#xD;2225-319X (Linking)</isbn><accession-num>28944176</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28944176</url></related-urls></urls><custom2>5602194</custom2><electronic-resource-num>10.21037/acs.2017.07.07</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 8-10 and Implantable cardioverter defibrillator ADDIN EN.CITE ;EndNote;;Cite;;Author;Mitsui;/Author;;Year;2016;/Year;;RecNum;3;/RecNum;;DisplayText;11;/DisplayText;;record;;rec-number;3;/rec-number;;foreign-keys;;key app=”EN” db-id=”ddpp9at0qefxziese9b5d2pgxt5ssss25e0d” timestamp=”1512192444″;3;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Mitsui, T.;/author;;author;Masuyama, H.;/author;;author;Ejiri, K.

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;/author;;author;Watkinson, O.;/author;;author;Pantazis, A.;/author;;author;Tome-Esteban, M.;/author;;author;Elliott, P. M.;/author;;author;McGregor, C. G. A.

;/author;;/authors;;/contributors;;auth-address;Institute of Cardiovascular Science, University College London, London, United Kingdom. Royal Brompton Hospital, Sydney St, Chelsea, London. Cardiology Clinical Academic Group, St George;apos;s University Hospitals NHS Foundation Trust, Tooting, London.;/auth-address;;titles;;title;Early and medium-term outcomes of Alfieri mitral valve repair in the management of systolic anterior motion during septal myectomy;/title;;secondary-title;J Card Surg;/secondary-title;;alt-title;Journal of cardiac surgery;/alt-title;;/titles;;periodical;;full-title;J Card Surg;/full-title;;abbr-1;Journal of cardiac surgery;/abbr-1;;/periodical;;alt-periodical;;full-title;J Card Surg;/full-title;;abbr-1;Journal of cardiac surgery;/abbr-1;;/alt-periodical;;dates;;year;2017;/year;;pub-dates;;date;Nov 23;/date;;/pub-dates;;/dates;;isbn;1540-8191 (Electronic) 0886-0440 (Linking);/isbn;;accession-num;29168204;/accession-num;;urls;;related-urls;;url;http://www.ncbi.

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1111/jocs.13239;/electronic-resource-num;;/record;;/Cite;;/EndNote;13. Though they increase survival and improve the quality of life, none of them have made progress in treating and reversing the pathogenesis of the disease. Since cardiac hypertrophy and interstitial fibrosis have prognostic value in this disease, the reversal of the two is expected to improve morbidity as well as decrease the risk of SCD in patients with HCM. Cardiac hypertrophy is thought to be potentially reversible and preventable ADDIN EN.CITE ;EndNote;;Cite;;Author;Marian;/Author;;Year;2000;/Year;;RecNum;4;/RecNum;;DisplayText;14;/DisplayText;;record;;rec-number;4;/rec-number;;foreign-keys;;key app=”EN” db-id=”0edasxaear9z04ewsayv2frgedxaz9dep90z” timestamp=”1511969872″;4;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Marian, A.

J.;/author;;/authors;;/contributors;;auth-address;Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. [email protected];/auth-address;;titles;;title;Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy;/title;;secondary-title;Lancet;/secondary-title;;alt-title;Lancet;/alt-title;;/titles;;periodical;;full-title;Lancet;/full-title;;abbr-1;Lancet;/abbr-1;;/periodical;;alt-periodical;;full-title;Lancet;/full-title;;abbr-1;Lancet;/abbr-1;;/alt-periodical;;pages;58-60;/pages;;volume;355;/volume;;number;9197;/number;;keywords;;keyword;Cardiomyopathy, Hypertrophic/*etiology/*genetics</keyword><keyword>Humans</keyword><keyword>Mutation</keyword><keyword>Myocardial Contraction/*genetics</keyword><keyword>Phenotype</keyword><keyword>Transforming Growth Factors/*genetics</keyword></keywords><dates><year>2000</year><pub-dates><date>Jan 1</date></pub-dates></dates><isbn>0140-6736 (Print) 0140-6736 (Linking)</isbn><accession-num>10615904</accession-num><urls><related-urls><url>http://www.ncbi.nlm.

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DATA 15. Many mechanisms are involved in the pathogenesis of the disease, which restricts targeting a specific pathway for its management. An alternative approach for successful management could be targeting mechanisms/pathways that are common to cardiac hypertrophic growth, such as oxidative stress pathways and specific cell signaling pathways, which are common to various forms of cardiac hypertrophy including HCM <EndNote><Cite><Author>Senthil</Author><Year>2005</Year><RecNum>26</RecNum><DisplayText>[16-20]</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1518762800">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Senthil, V.</author><author>Chen, S. N.</author><author>Tsybouleva, N.</author><author>Halder, T.</author><author>Nagueh, S. F.</author><author>Willerson, J. T.</author><author>Roberts, R.</author><author>Marian, A. J.</author></authors></contributors><auth-address>Department of Medicine, Baylor College of Medicine, One Baylor Plaza, 519D, Houston, TX 77030, USA.</auth-address><titles><title>Prevention of cardiac hypertrophy by atorvastatin in a transgenic rabbit model of human hypertrophic cardiomyopathy</title><secondary-title>Circ Res</secondary-title><alt-title>Circulation research</alt-title></titles><periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></periodical><alt-periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></alt-periodical><pages>285-92</pages><volume>97</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Animals, Genetically Modified</keyword><keyword>Apoptosis</keyword><keyword>Atorvastatin Calcium</keyword><keyword>Cardiomyopathy, Hypertrophic/*prevention &amp; control</keyword><keyword>Cholesterol/blood</keyword><keyword>DNA, Mitochondrial/analysis</keyword><keyword>Disease Models, Animal</keyword><keyword>Extracellular Signal-Regulated MAP Kinases/analysis</keyword><keyword>Female</keyword><keyword>Heptanoic Acids/*therapeutic use</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use</keyword><keyword>Hypertrophy, Left Ventricular/prevention &amp; control</keyword><keyword>Male</keyword><keyword>Myocytes, Cardiac/pathology</keyword><keyword>Myosin Heavy Chains/physiology</keyword><keyword>Oxidative Stress</keyword><keyword>Pyrroles/*therapeutic use</keyword><keyword>Rabbits</keyword><keyword>Ventricular Function, Left</keyword><keyword>p38 Mitogen-Activated Protein Kinases/analysis</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug 5</date></pub-dates></dates><isbn>1524-4571 (Electronic)&#xD;0009-7330 (Linking)</isbn><accession-num>16020756</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16020756</url></related-urls></urls><custom2>1201449</custom2><electronic-resource-num>10.1161/01.RES.0000177090.07296.ac</electronic-resource-num></record></Cite><Cite><Author>Marian</Author><Year>2006</Year><RecNum>25</RecNum><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1518762088">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Marian, A. J.</author><author>Senthil, V.</author><author>Chen, S. N.</author><author>Lombardi, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. amarian@bcm.tmc.edu</auth-address><titles><title>Antifibrotic effects of antioxidant N-acetylcysteine in a mouse model of human hypertrophic cardiomyopathy mutation</title><secondary-title>J Am Coll Cardiol</secondary-title><alt-title>Journal of the American College of Cardiology</alt-title></titles><periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></periodical><alt-periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></alt-periodical><pages>827-34</pages><volume>47</volume><number>4</number><keywords><keyword>Acetylcysteine/*therapeutic use</keyword><keyword>Animals</keyword><keyword>Antioxidants/*therapeutic use</keyword><keyword>Cardiomyopathy, Hypertrophic/diagnostic imaging/*drug</keyword><keyword>therapy/metabolism/pathology</keyword><keyword>Collagen/analysis</keyword><keyword>DNA/metabolism</keyword><keyword>DNA, Mitochondrial/metabolism</keyword><keyword>Echocardiography</keyword><keyword>Fibrosis</keyword><keyword>Gene Expression</keyword><keyword>Heart/drug effects</keyword><keyword>Lipid Peroxidation</keyword><keyword>Malondialdehyde/analysis</keyword><keyword>Matrix Metalloproteinase 1/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Myocardium/metabolism/pathology</keyword><keyword>Procollagen/genetics/metabolism</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword></keywords><dates><year>2006</year><pub-dates><date>Feb 21</date></pub-dates></dates><isbn>1558-3597 (Electronic)&#xD;0735-1097 (Linking)</isbn><accession-num>16487852</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16487852</url></related-urls></urls><custom2>2772865</custom2><electronic-resource-num>10.1016/j.jacc.2005.10.041</electronic-resource-num></record></Cite><Cite><Author>Tirouvanziam</Author><Year>2006</Year><RecNum>717</RecNum><record><rec-number>717</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493191694">717</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tirouvanziam, R.</author><author>Conrad, C. K.</author><author>Bottiglieri, T.</author><author>Herzenberg, L. A.</author><author>Moss, R. B.</author><author>Herzenberg, L. A.</author></authors></contributors><auth-address>Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. tirouvan@stanford.edu</auth-address><titles><title>High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>4628-33</pages><volume>103</volume><number>12</number><keywords><keyword>Acetylcysteine/*administration &amp; dosage</keyword><keyword>Administration, Oral</keyword><keyword>Adolescent</keyword><keyword>Antioxidants/metabolism</keyword><keyword>Child</keyword><keyword>Cystic Fibrosis/*drug therapy</keyword><keyword>Female</keyword><keyword>Glutathione/analysis/chemistry/*metabolism</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Neutrophils/*drug effects</keyword><keyword>Pancreatic Elastase/metabolism</keyword><keyword>Pneumonia/*drug therapy</keyword><keyword>Prodrugs/*administration &amp; dosage</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar 21</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>16537378</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16537378</url></related-urls></urls><custom2>1450222</custom2><electronic-resource-num>10.1073/pnas.0511304103</electronic-resource-num></record></Cite><Cite><Author>Takimoto, E.; Kass, D. A.</Author><Year>2007</Year><RecNum>715</RecNum><record><database name="My EndNote Library.enl" path="/Users/ma/Documents/My EndNote Library.enl">My EndNote Library.enl</database><source-app name="EndNote" version="17.0">EndNote</source-app><rec-number>715</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe">715</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Takimoto, E.</style></author><author><style face="normal" font="default" size="100%">Kass, D. A.</style></author></authors></contributors><auth-address><style face="normal" font="default" size="100%">Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.</style></auth-address><titles><title><style face="normal" font="default" size="100%">Role of oxidative stress in cardiac hypertrophy and remodeling</style></title><secondary-title><style face="normal" font="default" size="100%">Hypertension</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Hypertension</style></alt-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Hypertension</style></full-title><abbr-1><style face="normal" font="default" size="100%">Hypertension</style></abbr-1></periodical><alt-periodical><full-title><style face="normal" font="default" size="100%">Hypertension</style></full-title><abbr-1><style face="normal" font="default" size="100%">Hypertension</style></abbr-1></alt-periodical><pages><style face="normal" font="default" size="100%">241-8</style></pages><volume><style face="normal" font="default" size="100%">49</style></volume><number><style face="normal" font="default" size="100%">2</style></number><keywords><keyword><style face="normal" font="default" size="100%">Animals</style></keyword><keyword><style face="normal" font="default" size="100%">Cardiomegaly/etiology/*physiopathology</style></keyword><keyword><style face="normal" font="default" size="100%">Humans</style></keyword><keyword><style face="normal" font="default" size="100%">Hypertension/complications</style></keyword><keyword><style face="normal" font="default" size="100%">Mitochondria, Heart/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">NADPH Oxidase/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Nitric Oxide Synthase Type III/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Nitroso Compounds/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Oxidation-Reduction</style></keyword><keyword><style face="normal" font="default" size="100%">*Oxidative Stress</style></keyword><keyword><style face="normal" font="default" size="100%">Oxidoreductases/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Reactive Oxygen Species/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">*Ventricular Remodeling</style></keyword><keyword><style face="normal" font="default" size="100%">Xanthine Oxidase/metabolism</style></keyword></keywords><dates><year><style face="normal" font="default" size="100%">2007</style></year><pub-dates><date><style face="normal" font="default" size="100%">Feb</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">1524-4563 (Electronic) 0194-911X (Linking)</style></isbn><accession-num><style face="normal" font="default" size="100%">17190878</style></accession-num><notes><style face="normal" font="default" size="100%">Takimoto, Eiki Kass, David A eng AG18324/AG/NIA NIH HHS/ P01H077180/PHS HHS/ P01HL59408/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov&apos;t Review Dallas, Tex. : 1979 2006/12/28 09:00 Hypertension. 2007 Feb;49(2):241-8. Epub 2006 Dec 26.</style></notes><urls><related-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/17190878</style></url></related-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1161/01.HYP.0000254415.31362.a7</style></electronic-resource-num></record></Cite><Cite><Author>R</Author><Year>2009</Year><RecNum>709</RecNum><record><rec-number>709</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1492689322">709</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lombardi R</author><author>Rodriguez G</author><author>Chen SN</author><author>Ripplinger CM</author><author>Li W</author><author>Chen J</author><author>Willerson, J. T.</author><author>Betocchi, S.</author><author>Wickline SA</author><author>Efimov IR</author><author>Marian, A. J.</author></authors></contributors><titles><title>Resolution of Established Cardiac Hypertrophy and Fibrosis and Prevention of Systolic Dysfunction in a Transgenic Rabbit Model of Human Cardiomyopathy Through Thiol-Sensitive Mechanisms</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></periodical><edition>2009 Mar 2</edition><dates><year>2009</year></dates><urls></urls><custom2>PMC2773801</custom2><electronic-resource-num>10.1161/CIRCULATIONAHA.108.790501</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Senthil</Author><Year>2005</Year><RecNum>26</RecNum><DisplayText>[16-20]</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1518762800">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Senthil, V.</author><author>Chen, S. N.</author><author>Tsybouleva, N.</author><author>Halder, T.</author><author>Nagueh, S. F.</author><author>Willerson, J. T.</author><author>Roberts, R.</author><author>Marian, A. J.</author></authors></contributors><auth-address>Department of Medicine, Baylor College of Medicine, One Baylor Plaza, 519D, Houston, TX 77030, USA.</auth-address><titles><title>Prevention of cardiac hypertrophy by atorvastatin in a transgenic rabbit model of human hypertrophic cardiomyopathy</title><secondary-title>Circ Res</secondary-title><alt-title>Circulation research</alt-title></titles><periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></periodical><alt-periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></alt-periodical><pages>285-92</pages><volume>97</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Animals, Genetically Modified</keyword><keyword>Apoptosis</keyword><keyword>Atorvastatin Calcium</keyword><keyword>Cardiomyopathy, Hypertrophic/*prevention &amp; control</keyword><keyword>Cholesterol/blood</keyword><keyword>DNA, Mitochondrial/analysis</keyword><keyword>Disease Models, Animal</keyword><keyword>Extracellular Signal-Regulated MAP Kinases/analysis</keyword><keyword>Female</keyword><keyword>Heptanoic Acids/*therapeutic use</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use</keyword><keyword>Hypertrophy, Left Ventricular/prevention &amp; control</keyword><keyword>Male</keyword><keyword>Myocytes, Cardiac/pathology</keyword><keyword>Myosin Heavy Chains/physiology</keyword><keyword>Oxidative Stress</keyword><keyword>Pyrroles/*therapeutic use</keyword><keyword>Rabbits</keyword><keyword>Ventricular Function, Left</keyword><keyword>p38 Mitogen-Activated Protein Kinases/analysis</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug 5</date></pub-dates></dates><isbn>1524-4571 (Electronic)&#xD;0009-7330 (Linking)</isbn><accession-num>16020756</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16020756</url></related-urls></urls><custom2>1201449</custom2><electronic-resource-num>10.1161/01.RES.0000177090.07296.ac</electronic-resource-num></record></Cite><Cite><Author>Marian</Author><Year>2006</Year><RecNum>25</RecNum><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1518762088">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Marian, A. J.</author><author>Senthil, V.</author><author>Chen, S. N.</author><author>Lombardi, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. amarian@bcm.tmc.edu</auth-address><titles><title>Antifibrotic effects of antioxidant N-acetylcysteine in a mouse model of human hypertrophic cardiomyopathy mutation</title><secondary-title>J Am Coll Cardiol</secondary-title><alt-title>Journal of the American College of Cardiology</alt-title></titles><periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></periodical><alt-periodical><full-title>J Am Coll Cardiol</full-title><abbr-1>Journal of the American College of Cardiology</abbr-1></alt-periodical><pages>827-34</pages><volume>47</volume><number>4</number><keywords><keyword>Acetylcysteine/*therapeutic use</keyword><keyword>Animals</keyword><keyword>Antioxidants/*therapeutic use</keyword><keyword>Cardiomyopathy, Hypertrophic/diagnostic imaging/*drug</keyword><keyword>therapy/metabolism/pathology</keyword><keyword>Collagen/analysis</keyword><keyword>DNA/metabolism</keyword><keyword>DNA, Mitochondrial/metabolism</keyword><keyword>Echocardiography</keyword><keyword>Fibrosis</keyword><keyword>Gene Expression</keyword><keyword>Heart/drug effects</keyword><keyword>Lipid Peroxidation</keyword><keyword>Malondialdehyde/analysis</keyword><keyword>Matrix Metalloproteinase 1/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Myocardium/metabolism/pathology</keyword><keyword>Procollagen/genetics/metabolism</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword></keywords><dates><year>2006</year><pub-dates><date>Feb 21</date></pub-dates></dates><isbn>1558-3597 (Electronic)&#xD;0735-1097 (Linking)</isbn><accession-num>16487852</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16487852</url></related-urls></urls><custom2>2772865</custom2><electronic-resource-num>10.1016/j.jacc.2005.10.041</electronic-resource-num></record></Cite><Cite><Author>Tirouvanziam</Author><Year>2006</Year><RecNum>717</RecNum><record><rec-number>717</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493191694">717</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tirouvanziam, R.</author><author>Conrad, C. K.</author><author>Bottiglieri, T.</author><author>Herzenberg, L. A.</author><author>Moss, R. B.</author><author>Herzenberg, L. A.</author></authors></contributors><auth-address>Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. tirouvan@stanford.edu</auth-address><titles><title>High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>4628-33</pages><volume>103</volume><number>12</number><keywords><keyword>Acetylcysteine/*administration &amp; dosage</keyword><keyword>Administration, Oral</keyword><keyword>Adolescent</keyword><keyword>Antioxidants/metabolism</keyword><keyword>Child</keyword><keyword>Cystic Fibrosis/*drug therapy</keyword><keyword>Female</keyword><keyword>Glutathione/analysis/chemistry/*metabolism</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Neutrophils/*drug effects</keyword><keyword>Pancreatic Elastase/metabolism</keyword><keyword>Pneumonia/*drug therapy</keyword><keyword>Prodrugs/*administration &amp; dosage</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar 21</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>16537378</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16537378</url></related-urls></urls><custom2>1450222</custom2><electronic-resource-num>10.1073/pnas.0511304103</electronic-resource-num></record></Cite><Cite><Author>Takimoto, E.; Kass, D. A.</Author><Year>2007</Year><RecNum>715</RecNum><record><database name="My EndNote Library.enl" path="/Users/ma/Documents/My EndNote Library.enl">My EndNote Library.enl</database><source-app name="EndNote" version="17.0">EndNote</source-app><rec-number>715</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe">715</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Takimoto, E.</style></author><author><style face="normal" font="default" size="100%">Kass, D. A.</style></author></authors></contributors><auth-address><style face="normal" font="default" size="100%">Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.</style></auth-address><titles><title><style face="normal" font="default" size="100%">Role of oxidative stress in cardiac hypertrophy and remodeling</style></title><secondary-title><style face="normal" font="default" size="100%">Hypertension</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Hypertension</style></alt-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Hypertension</style></full-title><abbr-1><style face="normal" font="default" size="100%">Hypertension</style></abbr-1></periodical><alt-periodical><full-title><style face="normal" font="default" size="100%">Hypertension</style></full-title><abbr-1><style face="normal" font="default" size="100%">Hypertension</style></abbr-1></alt-periodical><pages><style face="normal" font="default" size="100%">241-8</style></pages><volume><style face="normal" font="default" size="100%">49</style></volume><number><style face="normal" font="default" size="100%">2</style></number><keywords><keyword><style face="normal" font="default" size="100%">Animals</style></keyword><keyword><style face="normal" font="default" size="100%">Cardiomegaly/etiology/*physiopathology</style></keyword><keyword><style face="normal" font="default" size="100%">Humans</style></keyword><keyword><style face="normal" font="default" size="100%">Hypertension/complications</style></keyword><keyword><style face="normal" font="default" size="100%">Mitochondria, Heart/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">NADPH Oxidase/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Nitric Oxide Synthase Type III/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Nitroso Compounds/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Oxidation-Reduction</style></keyword><keyword><style face="normal" font="default" size="100%">*Oxidative Stress</style></keyword><keyword><style face="normal" font="default" size="100%">Oxidoreductases/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">Reactive Oxygen Species/metabolism</style></keyword><keyword><style face="normal" font="default" size="100%">*Ventricular Remodeling</style></keyword><keyword><style face="normal" font="default" size="100%">Xanthine Oxidase/metabolism</style></keyword></keywords><dates><year><style face="normal" font="default" size="100%">2007</style></year><pub-dates><date><style face="normal" font="default" size="100%">Feb</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">1524-4563 (Electronic) 0194-911X (Linking)</style></isbn><accession-num><style face="normal" font="default" size="100%">17190878</style></accession-num><notes><style face="normal" font="default" size="100%">Takimoto, Eiki Kass, David A eng AG18324/AG/NIA NIH HHS/ P01H077180/PHS HHS/ P01HL59408/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov&apos;t Review Dallas, Tex. : 1979 2006/12/28 09:00 Hypertension. 2007 Feb;49(2):241-8. Epub 2006 Dec 26.</style></notes><urls><related-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/17190878</style></url></related-urls></urls><electronic-resource-num><style face="normal" font="default" size="100%">10.1161/01.HYP.0000254415.31362.a7</style></electronic-resource-num></record></Cite><Cite><Author>R</Author><Year>2009</Year><RecNum>709</RecNum><record><rec-number>709</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1492689322">709</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lombardi R</author><author>Rodriguez G</author><author>Chen SN</author><author>Ripplinger CM</author><author>Li W</author><author>Chen J</author><author>Willerson, J. T.</author><author>Betocchi, S.</author><author>Wickline SA</author><author>Efimov IR</author><author>Marian, A. J.</author></authors></contributors><titles><title>Resolution of Established Cardiac Hypertrophy and Fibrosis and Prevention of Systolic Dysfunction in a Transgenic Rabbit Model of Human Cardiomyopathy Through Thiol-Sensitive Mechanisms</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></periodical><edition>2009 Mar 2</edition><dates><year>2009</year></dates><urls></urls><custom2>PMC2773801</custom2><electronic-resource-num>10.1161/CIRCULATIONAHA.108.790501</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 16-20. Various medications that block the oxidative stress pathways have provided wonderful results in experimental animals, like N- Acetyl cysteine (NAC) have shown to reduce fibrosis together with reducing myocardial oxidative stress in mouse 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ADDIN EN.

CITE 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ADDIN EN.CITE.DATA 17, 21. HMG-CoA reductase inhibitors or statins having antioxidant effects <EndNote><Cite><Author>Oi</Author><Year>1999</Year><RecNum>727</RecNum><DisplayText>[22-25]</DisplayText><record><rec-number>727</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493195706">727</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Oi, S.</author><author>Haneda, T.</author><author>Osaki, J.</author><author>Kashiwagi, Y.</author><author>Nakamura, Y.</author><author>Kawabe, J.</author><author>Kikuchi, K.</author></authors></contributors><auth-address>First Department of Internal Medicine, Asahikawa Medical College, Japan.</auth-address><titles><title>Lovastatin prevents angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells</title><secondary-title>Eur J Pharmacol</secondary-title><alt-title>European journal of pharmacology</alt-title></titles><periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></periodical><alt-periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></alt-periodical><pages>139-48</pages><volume>376</volume><number>1-2</number><keywords><keyword>Angiotensin II/pharmacology/*physiology</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Calcium-Calmodulin-Dependent Protein Kinases/metabolism</keyword><keyword>Cardiomegaly/pathology/*prevention &amp; control</keyword><keyword>Cell Division/drug effects</keyword><keyword>Cell Membrane/physiology</keyword><keyword>Cells, Cultured</keyword><keyword>DNA/biosynthesis</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology</keyword><keyword>Lovastatin/*pharmacology</keyword><keyword>Myocardium/pathology</keyword><keyword>Naphthalenes/pharmacology</keyword><keyword>Pravastatin/pharmacology</keyword><keyword>Proto-Oncogene Proteins p21(ras)/metabolism/physiology</keyword><keyword>RNA/biosynthesis</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Simvastatin/pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>Jul 02</date></pub-dates></dates><isbn>0014-2999 (Print)&#xD;0014-2999 (Linking)</isbn><accession-num>10440099</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10440099</url></related-urls></urls></record></Cite><Cite><Author>Moriyama</Author><Year>2001</Year><RecNum>725</RecNum><record><rec-number>725</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493195600">725</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Moriyama, T.</author><author>Kawada, N.</author><author>Nagatoya, K.</author><author>Takeji, M.</author><author>Horio, M.</author><author>Ando, A.</author><author>Imai, E.</author><author>Hori, M.</author></authors></contributors><auth-address>Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, School of Health and Sport Sciences, Osaka University, Osaka, Japan. moriyama@medone.med.osaka-u.ac.jp</auth-address><titles><title>Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction</title><secondary-title>Kidney Int</secondary-title><alt-title>Kidney international</alt-title></titles><periodical><full-title>Kidney Int</full-title><abbr-1>Kidney international</abbr-1></periodical><alt-periodical><full-title>Kidney Int</full-title><abbr-1>Kidney international</abbr-1></alt-periodical><pages>2095-103</pages><volume>59</volume><number>6</number><keywords><keyword>Actins/genetics</keyword><keyword>Animals</keyword><keyword>Cholesterol/blood</keyword><keyword>Disease Models, Animal</keyword><keyword>Fatty Acids, Monounsaturated/*pharmacology</keyword><keyword>Fibrosis</keyword><keyword>Gene Expression/drug effects</keyword><keyword>Glycosylation End Products, Advanced/analysis</keyword><keyword>Heme Oxygenase (Decyclizing)/genetics/metabolism</keyword><keyword>Heme Oxygenase-1</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology</keyword><keyword>Indoles/*pharmacology</keyword><keyword>Kidney/enzymology/pathology</keyword><keyword>Membrane Proteins</keyword><keyword>Mice</keyword><keyword>Nephritis, Interstitial/drug therapy/metabolism/pathology</keyword><keyword>Oxidative Stress/*drug effects</keyword><keyword>Pravastatin/pharmacology</keyword><keyword>RNA, Messenger/analysis</keyword><keyword>Triglycerides/blood</keyword><keyword>Ureteral Obstruction/*drug therapy/*metabolism/pathology</keyword></keywords><dates><year>2001</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0085-2538 (Print)&#xD;0085-2538 (Linking)</isbn><accession-num>11380811</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11380811</url></related-urls></urls><electronic-resource-num>10.1046/j.1523-1755.2001.00724.x</electronic-resource-num></record></Cite><Cite><Author>Delbosc</Author><Year>2002</Year><RecNum>37</RecNum><record><rec-number>37</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515084141">37</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Delbosc, S.</author><author>Cristol, J. P.</author><author>Descomps, B.</author><author>Mimran, A.</author><author>Jover, B.</author></authors></contributors><auth-address>Groupe Rein Hypertension, Institut Universitaire de Recherche Clinique, Universite de Montpellier, France.</auth-address><titles><title>Simvastatin prevents angiotensin II-induced cardiac alteration and oxidative stress</title><secondary-title>Hypertension</secondary-title><alt-title>Hypertension</alt-title></titles><periodical><full-title>Hypertension</full-title><abbr-1>Hypertension</abbr-1></periodical><alt-periodical><full-title>Hypertension</full-title><abbr-1>Hypertension</abbr-1></alt-periodical><pages>142-7</pages><volume>40</volume><number>2</number><keywords><keyword>Angiotensin II/*pharmacology</keyword><keyword>Animals</keyword><keyword>Aorta, Thoracic/drug effects/metabolism</keyword><keyword>Body Weight/drug effects</keyword><keyword>Creatinine/blood</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Eating/drug effects</keyword><keyword>Hydrogen Peroxide/metabolism</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology</keyword><keyword>Lipids/blood</keyword><keyword>Male</keyword><keyword>Myocardium/*metabolism/pathology</keyword><keyword>Neutrophils/cytology/drug effects/metabolism</keyword><keyword>Oxidative Stress/*drug effects</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Reactive Oxygen Species/metabolism</keyword><keyword>Simvastatin/*pharmacology</keyword><keyword>Sodium/urine</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1524-4563 (Electronic)&#xD;0194-911X (Linking)</isbn><accession-num>12154104</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12154104</url></related-urls></urls></record></Cite><Cite><Author>Chen</Author><Year>2004</Year><RecNum>721</RecNum><record><rec-number>721</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493195362">721</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chen, M. S.</author><author>Xu, F. P.</author><author>Wang, Y. Z.</author><author>Zhang, G. P.</author><author>Yi, Q.</author><author>Zhang, H. Q.</author><author>Luo, J. D.</author></authors></contributors><auth-address>Department of Pharmacology, Guangzhou Medical College, Guangzhou 510182, China.</auth-address><titles><title>Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>889-96</pages><volume>37</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Aortic Coarctation/complications</keyword><keyword>Aortic Valve Stenosis/complications</keyword><keyword>Apoptosis/drug effects</keyword><keyword>Atrial Natriuretic Factor/biosynthesis/genetics</keyword><keyword>Cardiac Output, Low/etiology/*prevention &amp; control</keyword><keyword>Caspase 3</keyword><keyword>Caspases/metabolism</keyword><keyword>Chronic Disease</keyword><keyword>Heart Ventricles/cytology/pathology</keyword><keyword>Hydrogen Peroxide/pharmacology</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use</keyword><keyword>Hypertrophy, Left Ventricular/complications/*drug therapy/etiology</keyword><keyword>Male</keyword><keyword>Myocytes, Cardiac/drug effects</keyword><keyword>Oxidative Stress/*drug effects</keyword><keyword>RNA, Messenger/analysis/metabolism</keyword><keyword>Rats</keyword><keyword>Simvastatin/pharmacology/*therapeutic use</keyword><keyword>Superoxides/analysis/metabolism</keyword></keywords><dates><year>2004</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0022-2828 (Print)&#xD;0022-2828 (Linking)</isbn><accession-num>15380679</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15380679</url></related-urls></urls><electronic-resource-num>10.1016/j.yjmcc.2004.06.019</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Oi</Author><Year>1999</Year><RecNum>727</RecNum><DisplayText>[22-25]</DisplayText><record><rec-number>727</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493195706">727</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Oi, S.</author><author>Haneda, T.</author><author>Osaki, J.</author><author>Kashiwagi, Y.</author><author>Nakamura, Y.</author><author>Kawabe, J.</author><author>Kikuchi, K.</author></authors></contributors><auth-address>First Department of Internal Medicine, Asahikawa Medical College, Japan.</auth-address><titles><title>Lovastatin prevents angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells</title><secondary-title>Eur J Pharmacol</secondary-title><alt-title>European journal of pharmacology</alt-title></titles><periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></periodical><alt-periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></alt-periodical><pages>139-48</pages><volume>376</volume><number>1-2</number><keywords><keyword>Angiotensin II/pharmacology/*physiology</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Calcium-Calmodulin-Dependent Protein Kinases/metabolism</keyword><keyword>Cardiomegaly/pathology/*prevention &amp; control</keyword><keyword>Cell Division/drug effects</keyword><keyword>Cell Membrane/physiology</keyword><keyword>Cells, Cultured</keyword><keyword>DNA/biosynthesis</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology</keyword><keyword>Lovastatin/*pharmacology</keyword><keyword>Myocardium/pathology</keyword><keyword>Naphthalenes/pharmacology</keyword><keyword>Pravastatin/pharmacology</keyword><keyword>Proto-Oncogene Proteins p21(ras)/metabolism/physiology</keyword><keyword>RNA/biosynthesis</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Simvastatin/pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>Jul 02</date></pub-dates></dates><isbn>0014-2999 (Print)&#xD;0014-2999 (Linking)</isbn><accession-num>10440099</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10440099</url></related-urls></urls></record></Cite><Cite><Author>Moriyama</Author><Year>2001</Year><RecNum>725</RecNum><record><rec-number>725</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493195600">725</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Moriyama, T.</author><author>Kawada, N.</author><author>Nagatoya, K.</author><author>Takeji, M.</author><author>Horio, M.</author><author>Ando, A.</author><author>Imai, E.</author><author>Hori, M.</author></authors></contributors><auth-address>Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, School of Health and Sport Sciences, Osaka University, Osaka, Japan. moriyama@medone.med.osaka-u.ac.jp</auth-address><titles><title>Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction</title><secondary-title>Kidney Int</secondary-title><alt-title>Kidney international</alt-title></titles><periodical><full-title>Kidney Int</full-title><abbr-1>Kidney international</abbr-1></periodical><alt-periodical><full-title>Kidney Int</full-title><abbr-1>Kidney international</abbr-1></alt-periodical><pages>2095-103</pages><volume>59</volume><number>6</number><keywords><keyword>Actins/genetics</keyword><keyword>Animals</keyword><keyword>Cholesterol/blood</keyword><keyword>Disease Models, Animal</keyword><keyword>Fatty Acids, Monounsaturated/*pharmacology</keyword><keyword>Fibrosis</keyword><keyword>Gene Expression/drug effects</keyword><keyword>Glycosylation End Products, Advanced/analysis</keyword><keyword>Heme Oxygenase (Decyclizing)/genetics/metabolism</keyword><keyword>Heme Oxygenase-1</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology</keyword><keyword>Indoles/*pharmacology</keyword><keyword>Kidney/enzymology/pathology</keyword><keyword>Membrane Proteins</keyword><keyword>Mice</keyword><keyword>Nephritis, Interstitial/drug therapy/metabolism/pathology</keyword><keyword>Oxidative Stress/*drug effects</keyword><keyword>Pravastatin/pharmacology</keyword><keyword>RNA, Messenger/analysis</keyword><keyword>Triglycerides/blood</keyword><keyword>Ureteral Obstruction/*drug therapy/*metabolism/pathology</keyword></keywords><dates><year>2001</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0085-2538 (Print)&#xD;0085-2538 (Linking)</isbn><accession-num>11380811</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11380811</url></related-urls></urls><electronic-resource-num>10.1046/j.1523-1755.2001.00724.x</electronic-resource-num></record></Cite><Cite><Author>Delbosc</Author><Year>2002</Year><RecNum>37</RecNum><record><rec-number>37</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515084141">37</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Delbosc, S.</author><author>Cristol, J. P.</author><author>Descomps, B.</author><author>Mimran, A.</author><author>Jover, B.</author></authors></contributors><auth-address>Groupe Rein Hypertension, Institut Universitaire de Recherche Clinique, Universite de Montpellier, France.</auth-address><titles><title>Simvastatin prevents angiotensin II-induced cardiac alteration and oxidative stress</title><secondary-title>Hypertension</secondary-title><alt-title>Hypertension</alt-title></titles><periodical><full-title>Hypertension</full-title><abbr-1>Hypertension</abbr-1></periodical><alt-periodical><full-title>Hypertension</full-title><abbr-1>Hypertension</abbr-1></alt-periodical><pages>142-7</pages><volume>40</volume><number>2</number><keywords><keyword>Angiotensin II/*pharmacology</keyword><keyword>Animals</keyword><keyword>Aorta, Thoracic/drug effects/metabolism</keyword><keyword>Body Weight/drug effects</keyword><keyword>Creatinine/blood</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Eating/drug effects</keyword><keyword>Hydrogen Peroxide/metabolism</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology</keyword><keyword>Lipids/blood</keyword><keyword>Male</keyword><keyword>Myocardium/*metabolism/pathology</keyword><keyword>Neutrophils/cytology/drug effects/metabolism</keyword><keyword>Oxidative Stress/*drug effects</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Reactive Oxygen Species/metabolism</keyword><keyword>Simvastatin/*pharmacology</keyword><keyword>Sodium/urine</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1524-4563 (Electronic)&#xD;0194-911X (Linking)</isbn><accession-num>12154104</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12154104</url></related-urls></urls></record></Cite><Cite><Author>Chen</Author><Year>2004</Year><RecNum>721</RecNum><record><rec-number>721</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe" timestamp="1493195362">721</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chen, M. S.</author><author>Xu, F. P.</author><author>Wang, Y. Z.</author><author>Zhang, G. P.</author><author>Yi, Q.</author><author>Zhang, H. Q.</author><author>Luo, J. D.</author></authors></contributors><auth-address>Department of Pharmacology, Guangzhou Medical College, Guangzhou 510182, China.</auth-address><titles><title>Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>889-96</pages><volume>37</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Aortic Coarctation/complications</keyword><keyword>Aortic Valve Stenosis/complications</keyword><keyword>Apoptosis/drug effects</keyword><keyword>Atrial Natriuretic Factor/biosynthesis/genetics</keyword><keyword>Cardiac Output, Low/etiology/*prevention &amp; control</keyword><keyword>Caspase 3</keyword><keyword>Caspases/metabolism</keyword><keyword>Chronic Disease</keyword><keyword>Heart Ventricles/cytology/pathology</keyword><keyword>Hydrogen Peroxide/pharmacology</keyword><keyword>Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use</keyword><keyword>Hypertrophy, Left Ventricular/complications/*drug therapy/etiology</keyword><keyword>Male</keyword><keyword>Myocytes, Cardiac/drug effects</keyword><keyword>Oxidative Stress/*drug effects</keyword><keyword>RNA, Messenger/analysis/metabolism</keyword><keyword>Rats</keyword><keyword>Simvastatin/pharmacology/*therapeutic use</keyword><keyword>Superoxides/analysis/metabolism</keyword></keywords><dates><year>2004</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0022-2828 (Print)&#xD;0022-2828 (Linking)</isbn><accession-num>15380679</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15380679</url></related-urls></urls><electronic-resource-num>10.1016/j.yjmcc.2004.06.019</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.

DATA 22-25, have been experimented in transgenic rabbit models and have shown to reverse cardiac myocyte hypertrophy and fibrosis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 16, 26. Cardiac hypertrophy was prevented using Atorvastatin in transgenic Rabbit model 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ADDIN EN.CITE 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ADDIN EN.CITE.

DATA 16. Despite the wonderful results in experimental animals, none of these drugs that block oxidative stress pathways have shown a significant good results in 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ADDIN EN.CITE 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ADDIN EN.CITE.

DATA 16, 17. The reason for this could be different cell signaling pathways that are activated by oxidative stress in the pathogenesis of the disease. Targeting cell signaling pathways together with antioxidants working on them could be a reasonable approach in finding a cure for this disease.We report the importance of Oxidative stress in the phenotypic expression of hypertrophic cardiomyopathy.1.2. RESEARCH QUESTION;Is there increase in reactive oxygen species (ROS) in the heart of a patient with hypertrophic cardiomyopathy?1.

3. HYPOTHESIS;There is increase in oxidative stress that is high amount of ROS in the human hearts affected by hypertrophic cardiomyopathy.1.4. OBJECTIVES;1.

4.1. Overall research aimTo observe and prove the increase in the oxidative stress in the human hearts with hypertrophic cardiomyopathy as compared to the normal hearts.1.4.

2. Specific objectives- To investigate different amount of ROS in different chambers of the heart.- To investigate the difference in increase in increase of ROS in the patients with diastolic dysfunction and the ones having systolic dysfunction HCMCHAPTER 2: LITERATURE REVIEW2.1. HYPERTROPHIC CARDIOMYOPATHY (HCM)It is the most common inherited heart disease that leads to marked hypertrophy of the left ventricle, which cannot be explained by other co morbidities example hypertension. It is the most common cause of sudden cardiac death in young and affects 1 in 500 people in the general population ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B.

A.</author><author>Stevens, G. R.

</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights.

Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.S15717</electronic-resource-num></record></Cite></EndNote>27. As said, the heart muscle cells hypertrophy and cause the ventricle walls to thicken.

When the thickening blocks the blood flow out of the ventricle, it is known as obstructive hypertrophic cardiomyopathy. Sometimes the disease affects the hearts mitral valve and causes the blood to leak backwards through it. And sometimes the hypertrophied muscles doesn’t block the flow of blood, this is referred to as non-obstructive hypertrophic cardiomyopathy. As mentioned before HCM is a genetic disease that is caused by mutation in the contractile sarcomeric protein genes in its typical forms but can also be caused by mutation in the non-sarcomeric proteins like mutation in the potassium voltage gated channels (KCNQ4)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 ADDIN EN.

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Currently over 1500 genetic mutations are implicated in hypertrophic cardiomyopathy 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ADDIN EN.CITE.

DATA 29. About 2/3 of cases have familial origin but only 1/3 occur sporadically though still genetic and can be passed to the offspring ADDIN EN.CITE <EndNote><Cite><Author>Marian</Author><Year>2001</Year><RecNum>4</RecNum><DisplayText>3</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516105389″>4</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marian, A. J.</author><author>Roberts, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. [email protected]

edu</auth-address><titles><title>The molecular genetic basis for hypertrophic cardiomyopathy</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>655-70</pages><volume>33</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/metabolism/pathology</keyword><keyword>Disease Models, Animal</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Phenotype</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2828 (Print) 0022-2828 (Linking)</isbn><accession-num>11273720</accession-num><urls><related-urls><url>http://www.ncbi.nlm.

nih.gov/pubmed/11273720</url></related-urls></urls><custom2>2901497</custom2><electronic-resource-num>10.1006/jmcc.2001.1340</electronic-resource-num></record></Cite></EndNote>3. Common genes responsible for HCM are the beta myocin heavy chain (?-MyHC), myocin-binding protein- C (MyBP-C), cardiac troponin T (cTnT) and these three takes approximately ¾ of the HCM cases. Other rare ones are ?-tropomyocin, cardiac troponin-I, ?-cardiac actin, titin and essential and regulatory light chains ADDIN EN.CITE <EndNote><Cite><Author>Marian</Author><Year>2001</Year><RecNum>4</RecNum><DisplayText>3</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516105389″>4</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marian, A.

J.</author><author>Roberts, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. [email protected]</auth-address><titles><title>The molecular genetic basis for hypertrophic cardiomyopathy</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>655-70</pages><volume>33</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/metabolism/pathology</keyword><keyword>Disease Models, Animal</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Phenotype</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2828 (Print) 0022-2828 (Linking)</isbn><accession-num>11273720</accession-num><urls><related-urls><url>http://www.

ncbi.nlm.nih.gov/pubmed/11273720</url></related-urls></urls><custom2>2901497</custom2><electronic-resource-num>10.1006/jmcc.2001.1340</electronic-resource-num></record></Cite></EndNote>3.

According to the previous studies ?-MyHC gene mutation had the largest prevalence of about 50% of cases followed by MyBP-C of about 20% of cases ADDIN EN.CITE <EndNote><Cite><Author>Marian</Author><Year>2001</Year><RecNum>4</RecNum><DisplayText>3</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516105389″>4</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marian, A. J.</author><author>Roberts, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. [email protected]

tmc.edu</auth-address><titles><title>The molecular genetic basis for hypertrophic cardiomyopathy</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>655-70</pages><volume>33</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/metabolism/pathology</keyword><keyword>Disease Models, Animal</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Phenotype</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2828 (Print) 0022-2828 (Linking)</isbn><accession-num>11273720</accession-num><urls><related-urls><url>http://www.ncbi.

nlm.nih.gov/pubmed/11273720</url></related-urls></urls><custom2>2901497</custom2><electronic-resource-num>10.

1006/jmcc.2001.1340</electronic-resource-num></record></Cite></EndNote>3, but recent studies have found MyBP-C having the highest amount of mutation of about 51% followed by ?-MyHC of around 24%<EndNote><Cite><Author>Viswanathan</Author><Year>2017</Year><RecNum>3</RecNum><DisplayText>[29-31]</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1516103481">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Viswanathan, S. K.</author><author>Sanders, H. K.</author><author>McNamara, J. W.</author><author>Jagadeesan, A.</author><author>Jahangir, A.</author><author>Tajik, A. J.</author><author>Sadayappan, S.</author></authors></contributors><auth-address>Heart Lung Vascular Institute, Division of Cardiology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.&#xD;Department of Cell and Molecular Physiology, Center for Translational Research and Education, Health Sciences Division, Loyola University Chicago, Maywood, Illinois, United States of America.&#xD;Aurora Cardiovascular Services, St. Luke&apos;s Medical Center, Milwaukee, Wisconsin, United States of America.&#xD;Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Health Care, Milwaukee, Wisconsin, United States of America.</auth-address><titles><title>Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e0187948</pages><volume>12</volume><number>11</number><keywords><keyword>Adult</keyword><keyword>Cardiac Myosins/*genetics</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/physiopathology</keyword><keyword>Carrier Proteins/*genetics</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Mutation</keyword><keyword>Myosin Heavy Chains/*genetics</keyword><keyword>Penetrance</keyword><keyword>Phenotype</keyword><keyword>Severity of Illness Index</keyword></keywords><dates><year>2017</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>29121657</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/29121657</url></related-urls></urls><custom2>5679632</custom2><electronic-resource-num>10.1371/journal.pone.0187948</electronic-resource-num></record></Cite><Cite><Author>Liu</Author><Year>2013</Year><RecNum>5</RecNum><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1516108202">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu, W.</author><author>Liu, W.</author><author>Hu, D.</author><author>Zhu, T.</author><author>Ma, Z.</author><author>Yang, J.</author><author>Xie, W.</author><author>Li, C.</author><author>Li, L.</author><author>Yang, J.</author><author>Li, T.</author><author>Bian, H.</author><author>Tong, Q.</author></authors></contributors><auth-address>Heart Center, Peking University People&apos;s Hospital, Beijing, People&apos;s Republic of China.</auth-address><titles><title>Mutation spectrum in a large cohort of unrelated Chinese patients with hypertrophic cardiomyopathy</title><secondary-title>Am J Cardiol</secondary-title><alt-title>The American journal of cardiology</alt-title></titles><periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></periodical><alt-periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></alt-periodical><pages>585-9</pages><volume>112</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Age of Onset</keyword><keyword>Alleles</keyword><keyword>Asian Continental Ancestry Group/*genetics</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics</keyword><keyword>Carrier Proteins/*genetics</keyword><keyword>Case-Control Studies</keyword><keyword>Chi-Square Distribution</keyword><keyword>Child</keyword><keyword>Disease Progression</keyword><keyword>Echocardiography</keyword><keyword>Electrocardiography</keyword><keyword>Exons</keyword><keyword>Female</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Introns</keyword><keyword>Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Mutation</keyword><keyword>Myosin Heavy Chains/*genetics</keyword><keyword>Phenotype</keyword><keyword>Sarcomeres/genetics</keyword><keyword>Statistics, Nonparametric</keyword><keyword>Troponin T/*genetics</keyword></keywords><dates><year>2013</year><pub-dates><date>Aug 15</date></pub-dates></dates><isbn>1879-1913 (Electronic)&#xD;0002-9149 (Linking)</isbn><accession-num>23711808</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23711808</url></related-urls></urls><electronic-resource-num>10.1016/j.amjcard.2013.04.021</electronic-resource-num></record></Cite><Cite><Author>Fourey</Author><Year>2017</Year><RecNum>6</RecNum><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1516108300">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fourey, D.</author><author>Care, M.</author><author>Siminovitch, K. A.</author><author>Weissler-Snir, A.</author><author>Hindieh, W.</author><author>Chan, R. H.</author><author>Gollob, M. H.</author><author>Rakowski, H.</author><author>Adler, A.</author></authors></contributors><auth-address>From the Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada (D.F., A.W.-S., W.H., R.H.C., M.H.G., H.R., A.A.); Fred A. Litwin &amp; Family Center in Genetic Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada (M.C., K.A.S.).&#xD;From the Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada (D.F., A.W.-S., W.H., R.H.C., M.H.G., H.R., A.A.); Fred A. Litwin &amp; Family Center in Genetic Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada (M.C., K.A.S.). arnonadler@gmail.com.</auth-address><titles><title>Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy: Revisiting the Gene-Dose Effect</title><secondary-title>Circ Cardiovasc Genet</secondary-title><alt-title>Circulation. Cardiovascular genetics</alt-title></titles><periodical><full-title>Circ Cardiovasc Genet</full-title><abbr-1>Circulation. Cardiovascular genetics</abbr-1></periodical><alt-periodical><full-title>Circ Cardiovasc Genet</full-title><abbr-1>Circulation. Cardiovascular genetics</abbr-1></alt-periodical><volume>10</volume><number>2</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age of Onset</keyword><keyword>Cardiomyopathy, Hypertrophic/epidemiology/*genetics</keyword><keyword>Carrier Proteins/*genetics</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Mutation</keyword><keyword>Prevalence</keyword></keywords><dates><year>2017</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1942-3268 (Electronic)&#xD;1942-3268 (Linking)</isbn><accession-num>28420666</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28420666</url></related-urls></urls><electronic-resource-num>10.1161/CIRCGENETICS.116.001685</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Viswanathan</Author><Year>2017</Year><RecNum>3</RecNum><DisplayText>[29-31]</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1516103481">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Viswanathan, S. K.</author><author>Sanders, H. K.</author><author>McNamara, J. W.</author><author>Jagadeesan, A.</author><author>Jahangir, A.</author><author>Tajik, A. J.</author><author>Sadayappan, S.</author></authors></contributors><auth-address>Heart Lung Vascular Institute, Division of Cardiology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.&#xD;Department of Cell and Molecular Physiology, Center for Translational Research and Education, Health Sciences Division, Loyola University Chicago, Maywood, Illinois, United States of America.&#xD;Aurora Cardiovascular Services, St. Luke&apos;s Medical Center, Milwaukee, Wisconsin, United States of America.&#xD;Center for Integrative Research on Cardiovascular Aging (CIRCA), Aurora Health Care, Milwaukee, Wisconsin, United States of America.</auth-address><titles><title>Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e0187948</pages><volume>12</volume><number>11</number><keywords><keyword>Adult</keyword><keyword>Cardiac Myosins/*genetics</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/physiopathology</keyword><keyword>Carrier Proteins/*genetics</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Mutation</keyword><keyword>Myosin Heavy Chains/*genetics</keyword><keyword>Penetrance</keyword><keyword>Phenotype</keyword><keyword>Severity of Illness Index</keyword></keywords><dates><year>2017</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>29121657</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/29121657</url></related-urls></urls><custom2>5679632</custom2><electronic-resource-num>10.1371/journal.pone.0187948</electronic-resource-num></record></Cite><Cite><Author>Liu</Author><Year>2013</Year><RecNum>5</RecNum><record><rec-number>5</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1516108202">5</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu, W.</author><author>Liu, W.</author><author>Hu, D.</author><author>Zhu, T.</author><author>Ma, Z.</author><author>Yang, J.</author><author>Xie, W.</author><author>Li, C.</author><author>Li, L.</author><author>Yang, J.</author><author>Li, T.</author><author>Bian, H.</author><author>Tong, Q.</author></authors></contributors><auth-address>Heart Center, Peking University People&apos;s Hospital, Beijing, People&apos;s Republic of China.</auth-address><titles><title>Mutation spectrum in a large cohort of unrelated Chinese patients with hypertrophic cardiomyopathy</title><secondary-title>Am J Cardiol</secondary-title><alt-title>The American journal of cardiology</alt-title></titles><periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></periodical><alt-periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></alt-periodical><pages>585-9</pages><volume>112</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Age of Onset</keyword><keyword>Alleles</keyword><keyword>Asian Continental Ancestry Group/*genetics</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics</keyword><keyword>Carrier Proteins/*genetics</keyword><keyword>Case-Control Studies</keyword><keyword>Chi-Square Distribution</keyword><keyword>Child</keyword><keyword>Disease Progression</keyword><keyword>Echocardiography</keyword><keyword>Electrocardiography</keyword><keyword>Exons</keyword><keyword>Female</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Introns</keyword><keyword>Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Mutation</keyword><keyword>Myosin Heavy Chains/*genetics</keyword><keyword>Phenotype</keyword><keyword>Sarcomeres/genetics</keyword><keyword>Statistics, Nonparametric</keyword><keyword>Troponin T/*genetics</keyword></keywords><dates><year>2013</year><pub-dates><date>Aug 15</date></pub-dates></dates><isbn>1879-1913 (Electronic)&#xD;0002-9149 (Linking)</isbn><accession-num>23711808</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23711808</url></related-urls></urls><electronic-resource-num>10.1016/j.amjcard.2013.04.021</electronic-resource-num></record></Cite><Cite><Author>Fourey</Author><Year>2017</Year><RecNum>6</RecNum><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="0z9efa5ex2wd9re9s9tx992m99zfteaszxaz" timestamp="1516108300">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fourey, D.</author><author>Care, M.</author><author>Siminovitch, K. A.</author><author>Weissler-Snir, A.</author><author>Hindieh, W.</author><author>Chan, R. H.</author><author>Gollob, M. H.</author><author>Rakowski, H.</author><author>Adler, A.</author></authors></contributors><auth-address>From the Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada (D.F., A.W.-S., W.H., R.H.C., M.H.G., H.R., A.A.); Fred A. Litwin &amp; Family Center in Genetic Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada (M.C., K.A.S.).&#xD;From the Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada (D.F., A.W.-S., W.H., R.H.C., M.H.G., H.R., A.A.); Fred A. Litwin &amp; Family Center in Genetic Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada (M.C., K.A.S.). arnonadler@gmail.com.</auth-address><titles><title>Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy: Revisiting the Gene-Dose Effect</title><secondary-title>Circ Cardiovasc Genet</secondary-title><alt-title>Circulation. Cardiovascular genetics</alt-title></titles><periodical><full-title>Circ Cardiovasc Genet</full-title><abbr-1>Circulation. Cardiovascular genetics</abbr-1></periodical><alt-periodical><full-title>Circ Cardiovasc Genet</full-title><abbr-1>Circulation. Cardiovascular genetics</abbr-1></alt-periodical><volume>10</volume><number>2</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age of Onset</keyword><keyword>Cardiomyopathy, Hypertrophic/epidemiology/*genetics</keyword><keyword>Carrier Proteins/*genetics</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Mutation</keyword><keyword>Prevalence</keyword></keywords><dates><year>2017</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1942-3268 (Electronic)&#xD;1942-3268 (Linking)</isbn><accession-num>28420666</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28420666</url></related-urls></urls><electronic-resource-num>10.1161/CIRCGENETICS.116.001685</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 29-31.

Patients with HCM can be asymptomatic and some can have severe symptoms like cardiac arrhythmias especially Atrial fibrillation (AF), heart failure, exercise intolerance, syncope and even sudden cardiac death ADDIN EN.CITE <EndNote><Cite><Author>Marian</Author><Year>2001</Year><RecNum>4</RecNum><DisplayText>3</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516105389″>4</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marian, A. J.</author><author>Roberts, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

[email protected]</auth-address><titles><title>The molecular genetic basis for hypertrophic cardiomyopathy</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>655-70</pages><volume>33</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/metabolism/pathology</keyword><keyword>Disease Models, Animal</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Phenotype</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2828 (Print) 0022-2828 (Linking)</isbn><accession-num>11273720</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.

gov/pubmed/11273720</url></related-urls></urls><custom2>2901497</custom2><electronic-resource-num>10.1006/jmcc.2001.1340</electronic-resource-num></record></Cite></EndNote>3.

The presentation varies even for individuals carrying the same mutation 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ADDIN EN.CITE.

DATA 29. Pathologically, there is occurrence of myocyte hypertrophy, myocyte disarray and interstitial fibrosis. While cardiac hypertrophy and interstitial fibrosis are major determinant of morbidity and mortality, myocyte disarray is considered the pathological hallmark of HCM ADDIN EN.CITE <EndNote><Cite><Author>Marian</Author><Year>2001</Year><RecNum>4</RecNum><DisplayText>3</DisplayText><record><rec-number>4</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516105389″>4</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marian, A. J.

</author><author>Roberts, R.</author></authors></contributors><auth-address>Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. [email protected]</auth-address><titles><title>The molecular genetic basis for hypertrophic cardiomyopathy</title><secondary-title>J Mol Cell Cardiol</secondary-title><alt-title>Journal of molecular and cellular cardiology</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>655-70</pages><volume>33</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Cardiomyopathy, Hypertrophic/*genetics/metabolism/pathology</keyword><keyword>Disease Models, Animal</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Phenotype</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0022-2828 (Print) 0022-2828 (Linking)</isbn><accession-num>11273720</accession-num><urls><related-urls><url>http://www.ncbi.

nlm.nih.gov/pubmed/11273720</url></related-urls></urls><custom2>2901497</custom2><electronic-resource-num>10.1006/jmcc.

2001.1340</electronic-resource-num></record></Cite></EndNote>3. Figure SEQ Figure * ARABIC 1; histologic subtypes of the heart samples.A. Is a normal section of myocardium stained with Hematoxylin and Eosin (H& E), B.

H&E stained myocardial section of the heart with HCM showing the disorganized Architecture. C. This is the higher magnification of H&E stained heart with HCM that shows myocyte disarray. D. a Masson Trichome stained myocardial section from the heart with HCM that shows interstitial fibrosisThe management of hypertrophic cardiomyopathy is divided into Life style changes, Pharmacologic therapy and Therapy that relieve the symptoms of illness example, therapies for advanced heart failure and therapies for cardiac arrhythmias also surgical therapies to reduce the manifestation of the phenotype. In life style modification, patient should avoid strenuous exercise because even moderate intense physical activity may lead into syncope or even sudden cardiac death. This is because of systemic hypo perfusion secondary to decrease in systemic vascular resistance and outflow obstruction despite increase in heart contraction and heart rate.

Patient should also avoid volume depletion as this can decrease even more the outflow gradient and cause systemic hypo perfusion that can end up into syncope and sudden cardiac death ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B. A.</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.

</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.

gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.S15717</electronic-resource-num></record></Cite></EndNote>27.In pharmacologic management the following have been described;Beta-blockers; the beta-adrenergic blocking agents like propranolol, Nadolol Bisoprolol, have been experimented much. Due to their effect of reducing heart rate hence increase diastolic filling time, decreasing heart contraction and reducing ventricular stiffness, they have been shown to reduce symptoms like physiologic outflow obstruction, dyspnea on exertion, ventricular arrhythmias and even Angina. They are used in patients with and without outflow obstruction but the non-vasodilating beta-blockers are preferred for patient with obstructive HCM so as to avoid exacerbating outflow gradient ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B. A.

</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights.

Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.nlm.

nih.gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.

S15717</electronic-resource-num></record></Cite></EndNote>27.Non- dihydropyridine calcium channel blockers; the two most known drugs are verapamil and diltiazem. They function like beta-blockers by reducing heart rate and heart contraction.

Though there is improvement is some of the clinical outcome, there is no evidence in improvement in clinical outcome, reduction in sudden cardiac death and heart failure in using these drugs. They are used as optional drugs in patients with severe ouflow obstruction or severe heart failure in non-obstructive disease due to their vasodilatory effect in the peripheral vessels and negative inotropic effects respectively ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B. A.</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.

</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.

ncbi.nlm.nih.gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.

4137/CMC.S15717</electronic-resource-num></record></Cite></EndNote>27.Disopyramide; is a class IA antiarrhythmic medication that have been shown to reduce outflow gradients hence improve symptoms in patient with outflow obstruction but no role in patient without obstruction gradient. Despite its anticholinergic side effects and QTc prolongation, it remains an important pharmacologic option for symptomatic patient with high outflow gradient and those without improvement despite the use of above medications ADDIN EN.

CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B. A.</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights.

Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.

nlm.nih.gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.S15717</electronic-resource-num></record></Cite></EndNote>27. Angiotensin converting enzyme (ACE) inhibitors, Angiotensin receptor blockers (ARB’s) and aldosterone receptor antagonists, have shown to have important effect in phenotypic expression of HCM (myocyte hypertrophy, myocyte disarray and interstitial fibrosis) rather than improvement in clinical symptoms. These should be used with caution as they tend to reduce the afterload and augment the outflow gradient hence can worsen the symptoms ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B.

A.</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights.

Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.

S15717</electronic-resource-num></record></Cite></EndNote>27.Management of Atrial Fibrillation; this has management have two aims, rate versus rhythm control and reducing the risk of thromboembolism. Patient with AF and hemodynamic instability should undergo emergent direct current cardioversion.

In ventricular rate control, beta-blockers and non-dihydropyridine calcium channel blockers should be used. In case of poor rate control Amiodarone can successfully restore normal sinus rhythm. Due to proarrythmic properties in patients with hypertrophy, propafenone, 1C antiarrythmic medications and Fleicainide should not be used. All HCM patients having persistent and paroxysmal AF should be treated with oral anticoagulation therapy or rather antiplatelet agents (clopidogrel and Aspirin) though less effective compaired to the former ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B.

A.</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.

</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.

gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.S15717</electronic-resource-num></record></Cite></EndNote>27. Apart from medication, the electrophysiological devices that are used in the management of HCM they help to reduce sudden cardiac death and reduce the need for surgical myomectomy. These are;Defibrillator therapy, it is called implantable cardiovertor defibrillator (ICD) or automated implantable cardiovertor defibrillator (AICD). It monitors the heart rate and rhythm and delivers therapies in terms of electrical shock. It is implanted inside the body and performs defibrillation and even pacing of the heart and by so doing it is able to correct life threatening arrhythmias 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ADDIN EN.

CITE.DATA 32. It protects against sudden cardiac death secondary to ventricular fibrillation, ventricular tachycardia or bradycardia ADDIN EN.CITE <EndNote><Cite><Author>Wang</Author><Year>2017</Year><RecNum>7</RecNum><DisplayText>33</DisplayText><record><rec-number>7</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516762762″>7</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Wang, N.</author><author>Xie, A.</author><author>Tjahjono, R.</author><author>Tian, D.

H.</author><author>Phan, S.</author><author>Yan, T. D.

</author><author>Bajona, P.</author><author>Phan, K.</author></authors></contributors><auth-address>Collaborative Research (CORE) Group, Sydney, Australia. Faculty of Medicine, University of Sydney, Sydney, Australia.

Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Institute of Life Sciences, Sant&apos;Anna School of Advanced Studies, Pisa, Italy.</auth-address><titles><title>Implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: an updated systematic review and meta-analysis of outcomes and complications</title><secondary-title>Ann Cardiothorac Surg</secondary-title><alt-title>Annals of cardiothoracic surgery</alt-title></titles><periodical><full-title>Ann Cardiothorac Surg</full-title><abbr-1>Annals of cardiothoracic surgery</abbr-1></periodical><alt-periodical><full-title>Ann Cardiothorac Surg</full-title><abbr-1>Annals of cardiothoracic surgery</abbr-1></alt-periodical><pages>298-306</pages><volume>6</volume><number>4</number><dates><year>2017</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>2225-319X (Print) 2225-319X (Linking)</isbn><accession-num>28944170</accession-num><urls><related-urls><url>http://www.ncbi.

nlm.nih.gov/pubmed/28944170</url></related-urls></urls><custom2>5602202</custom2><electronic-resource-num>10.21037/acs.2017.07.05</electronic-resource-num></record></Cite></EndNote>33. Dual- chamber pacing, in here electrodes are inserted both in right atrium and right ventricle.

The atrial lead can sense the patient’s intrinsic P waves and stimulate the atrium when the atrial rate becomes too slow. The device provides atrial ventricular delay, which is analogous to PR interval seen in normal conduction. It maintains physiologic timing between atrial and ventricular systole. The device can reduce left ventricular outflow tract gradient hence relieve symptoms and regress hypertrophy in some patients ADDIN EN.

CITE <EndNote><Cite><Author>Nishimura</Author><Year>1997</Year><RecNum>9</RecNum><DisplayText>34</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516766030″>9</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Nishimura, R. A.</author><author>Symanski, J.

D.</author><author>Hurrell, D. G.

</author></authors></contributors><auth-address>Department of Internal Medicine, Mayo Clinic, Rochester, Minn, USA.</auth-address><titles><title>Images in cardiovascular medicine. Dual-chamber pacing in a patient with hypertrophic cardiomyopathy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></periodical><alt-periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></alt-periodical><pages>1701</pages><volume>96</volume><number>5</number><keywords><keyword>Cardiac Pacing, Artificial/*methods</keyword><keyword>Cardiomyopathy, Hypertrophic/complications/*therapy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Middle Aged</keyword><keyword>Ventricular Outflow Obstruction/etiology/physiopathology/therapy</keyword></keywords><dates><year>1997</year><pub-dates><date>Sep 2</date></pub-dates></dates><isbn>0009-7322 (Print) 0009-7322 (Linking)</isbn><accession-num>9315567</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9315567</url></related-urls></urls></record></Cite></EndNote>34. Despite its functioning, some studies have noted no beneficial effect nor relieve of symptoms when using this device 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 27, 35.Biventricular pacing, in here there are at least two leads, one into the right ventricle to stimulate the septum and another is inserted through the coronary sinus to pace the left ventricular apical wall. For patients with normal sinus rhythm, another lead is placed in the right atrium to facilitate synchrony with atrial contraction. The system is said to reduce outflow tract gradient and some studies have already demonstrated improvement of symptoms 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 27, 36.Despite medical therapy, some patients remain symptomatic with significant outflow obstruction and are symptomatic both during exercise and even at rest. These patients are candidates for septal- reduction technique. These are of two types; Septal ablation and surgical myectomy.Septal ablation; also known as percutaneous alcohol septal ablation performed by injecting absolute alcohol into the first septal perforator of the left anterior descending artery, which will cause controlled infarction of the hypertrophied septum therefore reduce its contractility and eventually even the thickness of the proximal inter-ventricular 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 27, 37. Patient symptomatic despite medical therapy is one of the criteria for alcohol septal ablation; other suggested ones are septal hypertrophy of 18mm or more and resting or provoked gradient of 50 mmHg or more 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 38. Surgical myectomy involves resection of the small amount of muscle (2-5) g from the proximal ventricular septum and some have modified it to be more widely and more distally, so as to widen the outflow tract and reduce the gradient ADDIN EN.CITE <EndNote><Cite><Author>Maron</Author><Year>2007</Year><RecNum>14</RecNum><DisplayText>39</DisplayText><record><rec-number>14</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516874015″>14</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Maron, B. J.</author></authors></contributors><auth-address>Minneapolis Heart Institute Foundation, 920 E 28th St, Ste 60, Minneapolis, MN 55407, USA. [email protected]</auth-address><titles><title>Controversies in cardiovascular medicine. Surgical myectomy remains the primary treatment option for severely symptomatic patients with obstructive hypertrophic cardiomyopathy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></periodical><alt-periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></alt-periodical><pages>196-206; discussion 206</pages><volume>116</volume><number>2</number><keywords><keyword>Cardiomyopathy, Hypertrophic/pathology/*surgery</keyword><keyword>Heart Failure/surgery</keyword><keyword>Heart Septum/pathology/*surgery</keyword><keyword>Humans</keyword><keyword>Informed Consent</keyword><keyword>Length of Stay</keyword><keyword>Reproducibility of Results</keyword><keyword>Risk Assessment</keyword><keyword>Survivors</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul 10</date></pub-dates></dates><isbn>1524-4539 (Electronic) 0009-7322 (Linking)</isbn><accession-num>17620519</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17620519</url></related-urls></urls><electronic-resource-num>10.1161/CIRCULATIONAHA.107.691378</electronic-resource-num></record></Cite></EndNote>39. Between the two, surgical myectomy have proven to be superior to alcohol septal ablation and the later has been taken as an alternative to the patients unfit for surgery. This might be due to the high risk of ventricular arrhythmias and heart block of septal ablation method 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ADDIN EN.CITE.DATA 27, 39.For patients with advanced heart failure, left ventricular assisted devices (LVAD) have somehow been explored and have been successful in a number of patients especially those who had concurrent septal myectomy to enlarge the left ventricular cavity size so as to accommodate the inflow cannula ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B. A.</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.S15717</electronic-resource-num></record></Cite></EndNote>27. Also, heart transplantation have been done for patients with life threatening arrhythmias and refractory heart failure with success ADDIN EN.CITE <EndNote><Cite><Author>Houston</Author><Year>2014</Year><RecNum>1</RecNum><DisplayText>27</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1516099875″>1</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Houston, B. A.</author><author>Stevens, G. R.</author></authors></contributors><auth-address>Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.</auth-address><titles><title>Hypertrophic cardiomyopathy: a review</title><secondary-title>Clin Med Insights Cardiol</secondary-title><alt-title>Clinical Medicine Insights. Cardiology</alt-title></titles><periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></periodical><alt-periodical><full-title>Clin Med Insights Cardiol</full-title><abbr-1>Clinical Medicine Insights. Cardiology</abbr-1></alt-periodical><pages>53-65</pages><volume>8</volume><number>Suppl 1</number><dates><year>2014</year></dates><isbn>1179-5468 (Print) 1179-5468 (Linking)</isbn><accession-num>25657602</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25657602</url></related-urls></urls><custom2>4309724</custom2><electronic-resource-num>10.4137/CMC.S15717</electronic-resource-num></record></Cite></EndNote>27.2.2. OXIDATIVE STRESSIt is an imbalance between oxidants and antioxidant system in the body. In other words, it is an imbalance between the production of oxygen free radicals and an inability of the body to counteract or neutralize them that leads into their excess in the body. The free radicals are the molecules that contain one or more unpaired electrons that make them highly reactive with other molecules in the body. Examples of free radicals are; Reactive oxygen species (ROS) which includes Superoxide anions (O-2), Hydrogen peroxide (H2O2) and Hydroxyl radicals (HO). Others are Nitric oxide (NO), Peroxynitrite Anions (ONOO-) etc. The mechanisms in which the free radicals are formed are as follows:Reduction- Oxidation reaction during metabolic processes; during normal metabolisms cells of the body generates energy, Adenosine triphosphate (ATP) by oxidative process. The end product is water from the combination of oxygen and hydrogen atoms. In this process four electrons are donated in four steps and in each step, partially reduced intermediates, which are free radicals, will be formed. Therefore free radicals will be formed by four steps reduction of oxygen as elaborated from the equation below.Figure SEQ Figure * ARABIC 2; four steps reduction of oxygen to form water. Note the free radical intermediates which produce increased oxidative stress when the reduction process is not complete.Radiant energy; absorption of ionizing radiation like ultra violet light and X- rays can cause formation of free radicals. Example water molecule can undergo radiolysis and produce hydroxyl radicals.Neutrophils function in oxygen dependent pathway or oxygen independent pathway in response to infection. In the oxygen dependent pathway, there is a process called “oxidative burst” in which, under NADPH oxidase, oxygen forms superoxide and then bleach (HOCl). Therefore there is a formation of free radicals.Transition metals; metals like Iron (Fe) and copper (Cu) do donate or accept free electrons during various intracellular reactions, through this they help to catalyze the formation of free radicals. Good example is the Fenton reaction during which hydroxyl radicals are formed from ferrous iron when combines with hydrogen peroxide. Figure SEQ Figure * ARABIC 3; Fenton reaction.Enzymatic metabolism of exogenous chemicals and drugs. Example, Acetaminophen that is metabolized by Cytochrome P450 (CP450) enzyme system, generate free radicals during the process. Therefore high doses of Acetaminophen will generate high dose of free radicals so does metabolism of Tetra hydrochloride.Nitrogen Oxide (NO) generated from endothelial cells, neurons, macrophages etc., combine with superoxide and forms Peroxynitrate (ONOO-).When the free radicals are formed, systems in the body work to remove and neutralize them and hence prevent oxidative stress caused by their excess. These are,Antioxidant system; Vitamin A, Vitamin C and Vitamin E, works as antioxidants together with Glutathione, which is found in the cytosol. Glutathione can block the formation of free radicals and can also inactivate them (Scavenger system).Metal carrier proteins; these are proteins binds, transport and store metals and make them inactive hence cannot for free radicals. These are such as Transferrin, Ferritin and Ceruloplasmin, where the first two are for iron and the last one is for copper. Free radicals scavenging system; it is a system of enzymes that neutralize the free radicals and hence reduce them in the body. There are three key enzymes in this system where each is responsible largely to a certain type of free radicals, these are, superoxide dismutase, catalase and glutathione peroxidase dealing with superoxide, hydrogen peroxide and hydroxyl radicals respectively. Catalase is found in peroxisomes and it breakdown hydrogen peroxide into oxygen and water. Superoxide dismutase converts superoxide into hydrogen peroxide. It has been said that, the ratio of oxidized glutathione to reduced glutathione reflects the oxidative state of the cell. Free radicals are known for their ability to cause cellular injury in the body. It does so in three types of reactions, these are, Lipid peroxidation in the membranes.Oxidative modification of proteins.DNA damage.In lipid peroxidation, free radicals particularly hydroxyl radicals, target double bonds of unsaturated fatty acids. This result into peroxides, which are unstable and reactive and can result into autocatalytic reaction, this reaction produces more and more free radicals and hence membrane damage. In oxidative modification of proteins, free radicals enhance oxidation of amino acid side chains of proteins and cause formation of covalent bonds example the disulphide bonds between proteins and form protein to protein cross linking. Oxidation can also occur in the protein backbone. The whole oxidation process tends to disrupt the active sites of enzymes (since they are also proteins) and reduces their functionality or even loss their function. In the structural proteins, the process can disrupt the structure and causes their conformation changes.The DNA damage is done by breaking down the DNA strands and can even form cross-linking between different strands. This leads to formation of mutant DNA strands that can lead cellular aging and even malignant transformation.Coming to the reactive oxygen species (ROS) in particular, there are some important functions, which have been noted like, activation of redox-sensitive transcription factors, such as AP-1, p53 and NF-?B and hence expression of pro-inflammatory cytokines ADDIN EN.CITE <EndNote><Cite><Author>Burton</Author><Year>2011</Year><RecNum>15</RecNum><DisplayText>40</DisplayText><record><rec-number>15</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1517218390″>15</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Burton, G. J.</author><author>Jauniaux, E.</author></authors></contributors><auth-address>Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. [email protected]</auth-address><titles><title>Oxidative stress</title><secondary-title>Best Pract Res Clin Obstet Gynaecol</secondary-title><alt-title>Best practice &amp; research. Clinical obstetrics &amp; gynaecology</alt-title></titles><periodical><full-title>Best Pract Res Clin Obstet Gynaecol</full-title><abbr-1>Best practice &amp; research. Clinical obstetrics &amp; gynaecology</abbr-1></periodical><alt-periodical><full-title>Best Pract Res Clin Obstet Gynaecol</full-title><abbr-1>Best practice &amp; research. Clinical obstetrics &amp; gynaecology</abbr-1></alt-periodical><pages>287-99</pages><volume>25</volume><number>3</number><keywords><keyword>Endoplasmic Reticulum/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Maternal-Fetal Exchange</keyword><keyword>Oxidative Stress/*physiology</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Complications/physiopathology</keyword><keyword>*Reactive Oxygen Species</keyword></keywords><dates><year>2011</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1532-1932 (Electronic) 1521-6934 (Linking)</isbn><accession-num>21130690</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21130690</url></related-urls></urls><custom2>3101336</custom2><electronic-resource-num>10.1016/j.bpobgyn.2010.10.016</electronic-resource-num></record></Cite></EndNote>40, activation of Protein Kinases hence control cellular functions like cell survival, proliferation and even cellular apoptosis depending on the receptor being activated ADDIN EN.CITE <EndNote><Cite><Author>Burton</Author><Year>2011</Year><RecNum>15</RecNum><DisplayText>40</DisplayText><record><rec-number>15</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1517218390″>15</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Burton, G. J.</author><author>Jauniaux, E.</author></authors></contributors><auth-address>Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. [email protected]</auth-address><titles><title>Oxidative stress</title><secondary-title>Best Pract Res Clin Obstet Gynaecol</secondary-title><alt-title>Best practice &amp; research. Clinical obstetrics &amp; gynaecology</alt-title></titles><periodical><full-title>Best Pract Res Clin Obstet Gynaecol</full-title><abbr-1>Best practice &amp; research. Clinical obstetrics &amp; gynaecology</abbr-1></periodical><alt-periodical><full-title>Best Pract Res Clin Obstet Gynaecol</full-title><abbr-1>Best practice &amp; research. Clinical obstetrics &amp; gynaecology</abbr-1></alt-periodical><pages>287-99</pages><volume>25</volume><number>3</number><keywords><keyword>Endoplasmic Reticulum/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Maternal-Fetal Exchange</keyword><keyword>Oxidative Stress/*physiology</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Complications/physiopathology</keyword><keyword>*Reactive Oxygen Species</keyword></keywords><dates><year>2011</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1532-1932 (Electronic) 1521-6934 (Linking)</isbn><accession-num>21130690</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21130690</url></related-urls></urls><custom2>3101336</custom2><electronic-resource-num>10.1016/j.bpobgyn.2010.10.016</electronic-resource-num></record></Cite></EndNote>40 and opening of ion channels particularly calcium release channels in endoplasmic reticulum membrane that leads into activation of calcium sensitive processes in the cell ADDIN EN.CITE <EndNote><Cite><Author>Hool</Author><Year>2007</Year><RecNum>16</RecNum><DisplayText>41</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1517221874″>16</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Hool, L. C.</author><author>Corry, B.</author></authors></contributors><auth-address>Discipline of Physiology, School of Biomedical, Biomolecular, and Chemical Sciences, The University of Western Australia, Crawley, Western Australia. [email protected]</auth-address><titles><title>Redox control of calcium channels: from mechanisms to therapeutic opportunities</title><secondary-title>Antioxid Redox Signal</secondary-title><alt-title>Antioxidants &amp; redox signaling</alt-title></titles><periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></periodical><alt-periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></alt-periodical><pages>409-35</pages><volume>9</volume><number>4</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Calcium/metabolism/physiology</keyword><keyword>Calcium Channel Blockers/pharmacology</keyword><keyword>Calcium Channels/genetics/*physiology</keyword><keyword>Humans</keyword><keyword>Models, Biological</keyword><keyword>Molecular Sequence Data</keyword><keyword>Oxidation-Reduction/drug effects</keyword><keyword>Reactive Oxygen Species/antagonists &amp; inhibitors/*metabolism</keyword></keywords><dates><year>2007</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1523-0864 (Print) 1523-0864 (Linking)</isbn><accession-num>17280484</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17280484</url></related-urls></urls><electronic-resource-num>10.1089/ars.2006.1446</electronic-resource-num></record></Cite></EndNote>41. Despite its useful functions, ROS have been implicated in a number of diseases like neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease ADDIN EN.CITE <EndNote><Cite><Author>Uttara</Author><Year>2009</Year><RecNum>21</RecNum><DisplayText>42</DisplayText><record><rec-number>21</rec-number><foreign-keys><key app=”EN” db-id=”0edasxaear9z04ewsayv2frgedxaz9dep90z” timestamp=”1512281626″>21</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Uttara, B.</author><author>Singh, A. V.</author><author>Zamboni, P.</author><author>Mahajan, R. T.</author></authors></contributors><auth-address>Department of Biotechnology, M. J. College, M. J. Road, Jalgaon- 425 001, India. [email protected]</auth-address><titles><title>Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options</title><secondary-title>Curr Neuropharmacol</secondary-title><alt-title>Current neuropharmacology</alt-title></titles><periodical><full-title>Curr Neuropharmacol</full-title><abbr-1>Current neuropharmacology</abbr-1></periodical><alt-periodical><full-title>Curr Neuropharmacol</full-title><abbr-1>Current neuropharmacology</abbr-1></alt-periodical><pages>65-74</pages><volume>7</volume><number>1</number><dates><year>2009</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1570-159X (Print) 1570-159X (Linking)</isbn><accession-num>19721819</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19721819</url></related-urls></urls><custom2>2724665</custom2><electronic-resource-num>10.2174/157015909787602823</electronic-resource-num></record></Cite></EndNote>42, various types of cancers due to destruction of the DNA and hence mutation of genes, various cardiovascular system diseases like in the development of atherosclerosis in the blood vessel walls, cardiomyopathies example diabetic 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ADDIN EN.CITE <EndNote><Cite><Author>Akhileshwar, V.; Patel, S. P.; Katyare, S. S.</Author><Year>2007</Year><RecNum>191</RecNum><DisplayText>[43, 44]</DisplayText><record><database name="My EndNote Library.enl" path="/Users/ma/Documents/My EndNote Library.enl">My EndNote Library.enl</database><source-app name="EndNote" version="17.0">EndNote</source-app><rec-number>191</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe">191</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Akhileshwar, V.</style></author><author><style face="normal" font="default" size="100%">Patel, S. P.</style></author><author><style face="normal" font="default" size="100%">Katyare, S. S.</style></author></authors></contributors><auth-address><style face="normal" font="default" size="100%">Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, 390 002 Vadodara, Gujarat India.</style></auth-address><titles><title><style face="normal" font="default" size="100%">Diabetic cardiomyopathy and reactive oxygen species (ROS) related parameters in male and female rats: A comparative study</style></title><secondary-title><style face="normal" font="default" size="100%">Indian J Clin Biochem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Indian journal of clinical biochemistry : IJCB</style></alt-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Indian J Clin Biochem</style></full-title><abbr-1><style face="normal" font="default" size="100%">Indian journal of clinical biochemistry : IJCB</style></abbr-1></periodical><alt-periodical><full-title><style face="normal" font="default" size="100%">Indian J Clin Biochem</style></full-title><abbr-1><style face="normal" font="default" size="100%">Indian journal of clinical biochemistry : IJCB</style></abbr-1></alt-periodical><pages><style face="normal" font="default" size="100%">84-90</style></pages><volume><style face="normal" font="default" size="100%">22</style></volume><number><style face="normal" font="default" size="100%">1</style></number><dates><year><style face="normal" font="default" size="100%">2007</style></year><pub-dates><date><style face="normal" font="default" size="100%">Mar</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">0970-1915 (Print) 0970-1915 (Linking)</style></isbn><accession-num><style face="normal" font="default" size="100%">23105658</style></accession-num><abstract><style face="normal" font="default" size="100%">Studies were carried out to examine and compare the effects of alloxan-diabetes on reactive oxygen species (ROS) related parameters in the heart from male and female rats. Effects of insulin treatment were also evaluated. The diabetic state severely compromised the ROS defense mechanism in the cardiac tissue and the effects were more pronounced in the female than in the male rats. There was several fold increase in the xanthine oxidase (XO) activity in general and the magnitude of increase was higher in the females; insulin treatment resulted in further increase in the XO activity. The glucose-6-phosphate dehydrogenase (G6PDH) and catalase activities decreased and the reduced glutathione (GSH) content in mitochondria was completely depleted in diabetic state with significant decrease in the GSH levels in the post-mitochondrial fraction; the effect was more pronounced in the females. The superoxide dismutase (SOD) and glutathione peroxidase (GPox) activities increased in the diabetic state to a greater extent in male rats. Insulin treatment had restorative action only on some parameters. In conclusion, our results suggest that diabetic state may further compromise the weak ROS defense systems in the heart thus initiating a lesion at the level of mitochondria which ultimately leads to cardiomyopathy and the effects are especially more pronounced in the females. Our results also pointed out that insulin treatment was ineffective in restoring ROS related parameters.</style></abstract><notes><style face="normal" font="default" size="100%">Akhileshwar, Vidya Patel, Samir P Katyare, Surendra S eng India 2007/03/01 00:00 Indian J Clin Biochem. 2007 Mar;22(1):84-90. doi: 10.1007/BF02912887.</style></notes><urls><related-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/23105658</style></url></related-urls></urls><custom2><style face="normal" font="default" size="100%">3454270</style></custom2><electronic-resource-num><style face="normal" font="default" size="100%">10.1007/BF02912887</style></electronic-resource-num></record></Cite><Cite><Author>Song, Y.; Du, Y.; Prabhu, S. D.; Epstein, P. N.</Author><Year>2007</Year><RecNum>241</RecNum><record><database name="My EndNote Library.enl" path="/Users/ma/Documents/My EndNote Library.enl">My EndNote Library.enl</database><source-app name="EndNote" version="17.0">EndNote</source-app><rec-number>241</rec-number><foreign-keys><key app="EN" db-id="fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe">241</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Song, Y.</style></author><author><style face="normal" font="default" size="100%">Du, Y.</style></author><author><style face="normal" font="default" size="100%">Prabhu, S. D.</style></author><author><style face="normal" font="default" size="100%">Epstein, P. N.</style></author></authors></contributors><auth-address><style face="normal" font="default" size="100%">Department of Pediatrics, University of Louisville and Louisville VAMC, Louisville, Kentucky, USA.</style></auth-address><titles><title><style face="normal" font="default" size="100%">Diabetic Cardiomyopathy in OVE26 Mice Shows Mitochondrial ROS Production and Divergence Between In Vivo and In Vitro Contractility</style></title><secondary-title><style face="normal" font="default" size="100%">Rev Diabet Stud</style></secondary-title><alt-title><style face="normal" font="default" size="100%">The review of diabetic studies : RDS</style></alt-title></titles><periodical><full-title><style face="normal" font="default" size="100%">Rev Diabet Stud</style></full-title><abbr-1><style face="normal" font="default" size="100%">The review of diabetic studies : RDS</style></abbr-1></periodical><alt-periodical><full-title><style face="normal" font="default" size="100%">Rev Diabet Stud</style></full-title><abbr-1><style face="normal" font="default" size="100%">The review of diabetic studies : RDS</style></abbr-1></alt-periodical><pages><style face="normal" font="default" size="100%">159-68</style></pages><volume><style face="normal" font="default" size="100%">4</style></volume><number><style face="normal" font="default" size="100%">3</style></number><dates><year><style face="normal" font="default" size="100%">2007</style></year><pub-dates><date><style face="normal" font="default" size="100%">Fall</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">1614-0575 (Electronic) 1613-6071 (Linking)</style></isbn><accession-num><style face="normal" font="default" size="100%">18084673</style></accession-num><abstract><style face="normal" font="default" size="100%">Many diabetic patients suffer from a cardiomyopathy that cannot be explained solely by poor coronary perfusion. This cardiomyopathy may be due to either organ-based damage like fibrosis, or to direct damage to cardiomyocytes. Mitochondrial-derived reactive oxygen species (ROS) have been proposed to contribute to this cardiomyopathy. To address these questions, we used the OVE26 mouse model of severe type 1 diabetes to measure contractility in isolated cardiomyocytes by edge detection and in vivo with echocardiography. We also assessed the source of ROS generation using both a general and a mitochondrial specific indicator. When contractility was assayed in freshly isolated myocytes, contraction was much stronger in control myocytes. However, contractility of normal myocytes became weaker during 24 hours of in vitro culture. In contrast, contractility of diabetic OVE26 myocytes remains stable during culture. Echocardiography revealed normal or hyperdynamic function in OVE26 hearts under basal conditions but with a sharply reduced response to isoproterenol, a beta-adrenergic agonist. For ROS generation, we found that ROS production in diabetic myocytes was elevated after exposure to either high glucose or angiotensin II (AngII). Superoxide detection with the mitochondrial sensor MitoSOX Red confirmed that mitochondria are a major source of ROS generation in diabetic myocytes. These results show that contractile deficits in OVE26 diabetic hearts are due primarily to cardiomyocyte impairment and that ROS from mitochondria are a cause of that impairment.</style></abstract><notes><style face="normal" font="default" size="100%">Song, Ye Du, Yibo Prabhu, Sumanth D Epstein, Paul N eng R01 DK073586/DK/NIDDK NIH HHS/ R01 HL062892/HL/NHLBI NIH HHS/ Germany 2007/12/18 09:00 Rev Diabet Stud. 2007 Fall;4(3):159-68. Epub 2007 Nov 10.</style></notes><urls><related-urls><url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/18084673</style></url></related-urls></urls><custom2><style face="normal" font="default" size="100%">2174063</style></custom2><electronic-resource-num><style face="normal" font="default" size="100%">10.1900/RDS.2007.4.159</style></electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 43, 44, and so does hypertrophic cardiomyopathy. Many researchers have shown the involvement of oxidative stress in hypertrophic cardiomyopathy, example, the expression of ALCAT1 (Acyl-CoA: Lysocardiolipin Acyltransferase-1), a lysocardiolipin acyltransferase that catalyzes the synthesis of cardiolipin important for oxidative phosphorylation in the mitochondrial membrane, was highly unregulated and caused severe oxidative stress in the cardiac cells with hypertrophic cardiomyopathy 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 45. Also, Celecoxib, a cyclooxygenase-2 non-steroid anti-inflammatory drug that have antioxidant effect, was shown to prevent cardiac hypertrophy, proved by reduction in Malondialdehyde, an oxidative stress maker during timely treatment with the drug 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 46.Though a straightforward pathway on how it causes hypertrophic cardiomyopathy is not yet clear, its action on different cell signaling pathway responsible for the development of HCM could answer the question. There are soo many cell signaling pathways in the human body cells that are responsible for various physiological pathways, disregulation of these pathway may lead into serious conditions like HCM. The pathways well studied in causing hypertrophic cardiomyopathy are Mitogen activated protein kinase signaling pathway (MAPK pathway), Phosphoinositide 3-kinase (PI3K-AKT) signaling pathway, Ca2+/calcineurin/NF-AT signaling pathway and Nuclear factor kappa- light- chain- enhancer of activated B cell (NF-kB) signaling pathway and all this have been shown to be activated by ROS in their process of causing cardiac hypertrophy. 2.2.1. OXIDATIVE STRESS AND HCMThere has been evidence in the increased amount of reactive oxygen species in the serum and heart muscles of patients with hypertrophic cardiomyopathy. Various theories exist concerning the increase in the oxidative stress in the heart and serum of patient with hypertrophic cardiomyopathy. The abnormalities in the Ca2+ handling by the mitochondriaDuring the process of contraction calcium induces calcium release from the endoplasmic reticulum, the calcium influx in the cytoplasm cause the muscle contraction by binding the thin filament regulatory protein troponin C. At the same time, calcium release from the sarcoplasmic reticulum stimulates ATP production from the mitochondria due to their close proximity. The latter is possible through mitochondrial calcium uniporter and the ability of mitochondrial matrix Ca2+ to control enzymes in the TCA (Tricarboxylic acid) cycle that yields reduced NADH that enter the electron transport chain and later converted to NADPH and reduce the oxidative stress in the process, so doing the anti-oxidant function. Mitochondrial Ca2+ also stimulates mitochondrial ATP synthase that eventually produces ATP. The amount of matrix calcium is affected by the amount of sodium in the cytoplasm. In the failing hearts as well as the hearts with HCM, it has been reported to have high amount cytosolic Na+ that increase the activity of mitochondrial Na+ – Ca2+ exchanger and hence a lot of Ca2+ is exported out of the mitochondria impairing the above activities and ultimately increase in the oxidative stress of the heart muscles ADDIN EN.CITE <EndNote><Cite><Author>Vakrou</Author><Year>2014</Year><RecNum>31</RecNum><DisplayText>6</DisplayText><record><rec-number>31</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1519198074″>31</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Vakrou, S.</author><author>Abraham, M. R.</author></authors></contributors><auth-address>Division of Cardiology, School of Medicine, Johns Hopkins University Baltimore, MD, USA.</auth-address><titles><title>Hypertrophic cardiomyopathy: a heart in need of an energy bar?</title><secondary-title>Front Physiol</secondary-title><alt-title>Frontiers in physiology</alt-title></titles><periodical><full-title>Front Physiol</full-title><abbr-1>Frontiers in physiology</abbr-1></periodical><alt-periodical><full-title>Front Physiol</full-title><abbr-1>Frontiers in physiology</abbr-1></alt-periodical><pages>309</pages><volume>5</volume><dates><year>2014</year></dates><isbn>1664-042X (Print) 1664-042X (Linking)</isbn><accession-num>25191275</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25191275</url></related-urls></urls><custom2>4137386</custom2><electronic-resource-num>10.3389/fphys.2014.00309</electronic-resource-num></record></Cite></EndNote>6.Impaired Mitochondrial Oxidative phosphorylation.During the normal oxidative phosphorylation that occurs in the inner mitochondrial membrane, electrons are transported in the series of structural protein complexes known as electron transport chain. There are five protein complexes; complex I (NADH dehydrogenase), complex II (Succinate dehydrogenase), complex III (Cytochrome C oxyreductase), Complex IV (Cytochrome oxidase) and Complex V (ATP synthase). The electrons are carried from the glycolysis, Preparatory stapes and the Creb’s cycle in the form of NADH and FADH2. The final electron acceptor in the process is O2, which is reduced to form water. And during the electron transport process, the H+ are being pumped out to the inter-membranous region at the complex proteins, producing the proton gradient, which then enter back the mitochondrial matrix due to their gradient through the complex V (ATP synthase) and harness ATP in the process where 4H+ will produce 1ATP molecule ADDIN EN.CITE <EndNote><Cite><Author>Fosslien</Author><Year>2003</Year><RecNum>35</RecNum><DisplayText>47</DisplayText><record><rec-number>35</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1519224638″>35</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Fosslien, E.</author></authors></contributors><auth-address>Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA. [email protected]</auth-address><titles><title>Review: Mitochondrial medicine–cardiomyopathy caused by defective oxidative phosphorylation</title><secondary-title>Ann Clin Lab Sci</secondary-title><alt-title>Annals of clinical and laboratory science</alt-title></titles><periodical><full-title>Ann Clin Lab Sci</full-title><abbr-1>Annals of clinical and laboratory science</abbr-1></periodical><alt-periodical><full-title>Ann Clin Lab Sci</full-title><abbr-1>Annals of clinical and laboratory science</abbr-1></alt-periodical><pages>371-95</pages><volume>33</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Cardiomyopathies/*etiology/therapy</keyword><keyword>Energy Metabolism</keyword><keyword>Humans</keyword><keyword>Mitochondria, Heart/genetics/*metabolism</keyword><keyword>Myocardium/metabolism</keyword><keyword>*Oxidative Phosphorylation</keyword></keywords><dates><year>2003</year><pub-dates><date>Fall</date></pub-dates></dates><isbn>0091-7370 (Print) 0091-7370 (Linking)</isbn><accession-num>14584751</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14584751</url></related-urls></urls></record></Cite></EndNote>47. In HCM, there is impairment in the oxidative phosphorylation reported in various studies; the process leads to the increase in the amount of reactive oxygen species in the heart muscles and increase in the oxidative damage 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 48. Oxidative phosphorylation can be impaired by various causes, common ones reported are the nuclear gene mutation or mitochondrial gene mutation, and these mutations cause abnormalities in the mitochondria and its protein complexes responsible for oxidative phosphorylation. Various patients with HCM have been reported to have defects in the protein complexes in the mitochondria responsible for the oxidative phosphorylation. The common mutations have been mutation in the complex I which takes about 1/3 of cases. And these mutations have been found in the cardiac muscles ADDIN EN.CITE <EndNote><Cite><Author>Holmgren</Author><Year>2003</Year><RecNum>33</RecNum><DisplayText>49</DisplayText><record><rec-number>33</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1519223173″>33</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Holmgren, D.</author><author>Wahlander, H.</author><author>Eriksson, B. O.</author><author>Oldfors, A.</author><author>Holme, E.</author><author>Tulinius, M.</author></authors></contributors><auth-address>Division of Pediatric Cardiology, The Queen Silvia Children&apos;s Hospital, Goteborg, Sweden. [email protected]</auth-address><titles><title>Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings</title><secondary-title>Eur Heart J</secondary-title><alt-title>European heart journal</alt-title></titles><periodical><full-title>Eur Heart J</full-title><abbr-1>European heart journal</abbr-1></periodical><alt-periodical><full-title>Eur Heart J</full-title><abbr-1>European heart journal</abbr-1></alt-periodical><pages>280-8</pages><volume>24</volume><number>3</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Cardiomyopathy, Hypertrophic/*etiology/pathology</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Echocardiography, Doppler/methods</keyword><keyword>Electrocardiography/methods</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Mitochondrial Diseases/*complications/pathology</keyword><keyword>Prognosis</keyword><keyword>Survival Analysis</keyword></keywords><dates><year>2003</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0195-668X (Print) 0195-668X (Linking)</isbn><accession-num>12590906</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12590906</url></related-urls></urls></record></Cite></EndNote>49 through endocardial biopsies in patients with idiopathic HCM. Mutations that cause complex II abnormalities have also been found in patients with HCM 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 50. Mutation that cause abnormalities in the ATP synthase 6 subunit of complex V have also been found in the patients with HCM and this mutation were present in the heart and not in the other parts of the body like the liver 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 48Slow generation of anti-oxidant enzymes by the cardiomyocytes, which exposes the heart to high risk of free radical injury. This was proved right by the experiment on exercising mice. The theory have never been proved in human heart, but if so could be a significant cause of increased oxidative stress in the hearts with HCM since mutation in the sarcomere cause increase in their energy cost and hence excessive sarcomere energy use.Low activity of catalase, as was explained before, catalase is an enzyme that is present in a large number of living cells and acts as antioxidants by reducing the cellular oxidative stress by breaking down hydrogen peroxide into water and oxygen molecules. There has been a report on the reduction on the amount of catalase in the porcine hearts with HCM, which lead into oxidative damage of the heart muscles 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 51.ROS acts on different signaling pathways to cause the phenotypes present in HCM commonly ones being cardiac hypertrophy and interstitial fibrosis. The common pathways that have been studies thoroughly which are activated by ROS are, MAPK signaling pathway, Akt/mTor signaling pathway, calcineurin/NF-AT signaling pathway and NF-kB signaling pathway. All these are activated in hypertrophic cardiomyopathy and so does ROS plays a great role in activating them already proved in other conditions. 2.2.2. ROS, SIGNALING PATHWAYS AND HCM 2.2.2.1. MAPK signaling pathwayMitogen-activated protein kinase (MAPK) also called Ras-Raf-MEK-ERK signaling pathways; belong to a family of Serine-Threonine protein kinases. It consist of a small G-protein (RAS) and three protein kinases (RAF, MEK, ERK) ADDIN EN.CITE <EndNote><Cite><Author>McCain</Author><Year>2013</Year><RecNum>78</RecNum><DisplayText>52</DisplayText><record><rec-number>78</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1515761591″>78</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>McCain, J.</author></authors></contributors><titles><title>The MAPK (ERK) Pathway: Investigational Combinations for the Treatment Of BRAF-Mutated Metastatic Melanoma</title><secondary-title>P T</secondary-title><alt-title>P &amp; T : a peer-reviewed journal for formulary management</alt-title></titles><periodical><full-title>P T</full-title><abbr-1>P &amp; T : a peer-reviewed journal for formulary management</abbr-1></periodical><alt-periodical><full-title>P T</full-title><abbr-1>P &amp; T : a peer-reviewed journal for formulary management</abbr-1></alt-periodical><pages>96-108</pages><volume>38</volume><number>2</number><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1052-1372 (Print) 1052-1372 (Linking)</isbn><accession-num>23599677</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23599677</url></related-urls></urls><custom2>3628180</custom2></record></Cite></EndNote>52 which sequentially phosphorylates each other in response to a particular stimuli like growth factors, cellular stress and cytokines. Upon ligand binding on the cell membrane receptors like tyrosine kinase or G-protein coupled receptors, the receptor signaling complex is formed that activates RAS by converting GDP bound RAS into GTP. RAS activates c-RAF, which phosphorylate and activate MEK1/2. The latter activate ERK1/2. ERKs do a lot of activities in the cytoplasm and nucleus and one most important is phosphorylation of transcription factors like Myc and regulates gene expression. By so doing the pathway is able to regulate a vast amount of processes in the body like cell growth and development, differentiation and cellular adaptations ADDIN EN.CITE <EndNote><Cite><Author>Orton</Author><Year>2005</Year><RecNum>79</RecNum><DisplayText>53</DisplayText><record><rec-number>79</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1515761722″>79</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Orton, R. J.</author><author>Sturm, O. E.</author><author>Vyshemirsky, V.</author><author>Calder, M.</author><author>Gilbert, D. R.</author><author>Kolch, W.</author></authors></contributors><auth-address>Bioinformatics Research Centre, Department of Computing Science, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.</auth-address><titles><title>Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway</title><secondary-title>Biochem J</secondary-title><alt-title>The Biochemical journal</alt-title></titles><periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></periodical><alt-periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></alt-periodical><pages>249-61</pages><volume>392</volume><number>Pt 2</number><keywords><keyword>Animals</keyword><keyword>*Computer Simulation</keyword><keyword>*MAP Kinase Signaling System</keyword><keyword>Mitogen-Activated Protein Kinase Kinases/*metabolism</keyword><keyword>*Models, Biological</keyword><keyword>Receptor Protein-Tyrosine Kinases/*metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Dec 1</date></pub-dates></dates><isbn>1470-8728 (Electronic) 0264-6021 (Linking)</isbn><accession-num>16293107</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16293107</url></related-urls></urls><custom2>1316260</custom2><electronic-resource-num>10.1042/BJ20050908</electronic-resource-num></record></Cite></EndNote>53. The pathway is deactivated by deactivating RAS through GTpase activating proteins (GAPs), these convert GTP of RAS back to GDP which is its inactive form. MAPK superfamily is divided in subfamilies known as extracellular responsive kinases (ERKs) and the two “stress-responsive” MAPK subfamilies, namely, the c-Jun N-terminal kinases (JNKs) and the p38-MAPKs 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ADDIN EN.CITE.DATA 54-56. These are named so due to their induction by physical, chemical and physiological stressors such as ultraviolet (UV) light, oxidative stress, osmotic shock, infection, and cytokines ADDIN EN.CITE <EndNote><Cite><Author>Kyriakis</Author><Year>2001</Year><RecNum>877</RecNum><DisplayText>57</DisplayText><record><rec-number>877</rec-number><foreign-keys><key app=”EN” db-id=”fxr5waddv5afa0ee0e9xdvtesevf9s55fvwe” timestamp=”1497058557″>877</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Kyriakis, J. M.</author><author>Avruch, J.</author></authors></contributors><auth-address>Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02129, USA. [email protected]</auth-address><titles><title>Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation</title><secondary-title>Physiol Rev</secondary-title><alt-title>Physiological reviews</alt-title></titles><periodical><full-title>Physiol Rev</full-title><abbr-1>Physiological reviews</abbr-1></periodical><alt-periodical><full-title>Physiol Rev</full-title><abbr-1>Physiological reviews</abbr-1></alt-periodical><pages>807-69</pages><volume>81</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Cytokines/physiology</keyword><keyword>Humans</keyword><keyword>Inflammation/*physiopathology</keyword><keyword>MAP Kinase Signaling System/*physiology</keyword><keyword>Mammals</keyword><keyword>Mitogen-Activated Protein Kinases/*metabolism</keyword><keyword>Stress, Physiological/*physiopathology</keyword><keyword>p38 Mitogen-Activated Protein Kinases</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0031-9333 (Print) 0031-9333 (Linking)</isbn><accession-num>11274345</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11274345</url></related-urls></urls></record></Cite></EndNote>57. Figure SEQ Figure * ARABIC 4; The MAPK signaling pathway,.Figure shows the intermediary downstream effectors and the end action produced by the pathway.Involvement of MAPK signaling in the pathogenesis of HCM have largely been proven and the majority of disease happen due to mutation of genes coding for RAS and RAF proteins as described well by Bruce et al who explained RAS and RAF 1 mutation in HCM. Most of these mutations cause over activation of ERK1/2 that later lead into HCM 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58, 59. In these cases gene therapy or blocking the over activated pathway could be a proper way forward, this was well demonstrated by Bruce and colleague, where MEK inhibitors prevented and even reversed the development of HCM 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58. In a transgenic rabbit model of ?-MyHC HCM, ERK1/2 were highly activated, upon treatment with simvastatin, cardiac hypertrophy and interstitial fibrosis were reduced and the cardiac function improved significantly compared to the control groups. Simvastatin acted by reducing the level of activated ERK1/2 and no effect was reported on RAS, while in the same type of model, Atorvastatin had the same effect but through inhibition of RAS 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 16, 26. MAPK signaling has been reported to participate largely in the cardiac hypertrophy even in cases, which are not classical HCM, this was proved by resultant inhibition of cardiac hypertrophy by MEK inhibitors and RAF inhibitors after giving hypertrophic agonists (Endothelin 1 and Phenyephrine) which activated MAPK signaling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 60.On the other hand, ROS (oxidative stress) have been reported to play a greater role in the activation of MAPK signaling pathway. The activation is done mostly through RAS protein. RAS contains six cysteine residues four of which are on the surface and are the active ones ADDIN EN.CITE <EndNote><Cite><Author>Mallis</Author><Year>2001</Year><RecNum>5</RecNum><DisplayText>61</DisplayText><record><rec-number>5</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1512316477″>5</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Mallis, R. J.</author><author>Buss, J. E.</author><author>Thomas, J. A.</author></authors></contributors><auth-address>Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, U.S.A.</auth-address><titles><title>Oxidative modification of H-ras: S-thiolation and S-nitrosylation of reactive cysteines</title><secondary-title>Biochem J</secondary-title><alt-title>The Biochemical journal</alt-title></titles><periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></periodical><alt-periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></alt-periodical><pages>145-53</pages><volume>355</volume><number>Pt 1</number><keywords><keyword>3T3 Cells</keyword><keyword>Animals</keyword><keyword>Cysteine/*metabolism</keyword><keyword>Electrophoresis, Polyacrylamide Gel</keyword><keyword>Mice</keyword><keyword>Nitroso Compounds/*metabolism</keyword><keyword>Oncogene Protein p21(ras)/chemistry/*metabolism</keyword><keyword>Oxidation-Reduction</keyword><keyword>Precipitin Tests</keyword><keyword>Sulfhydryl Compounds/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 1</date></pub-dates></dates><isbn>0264-6021 (Print) 0264-6021 (Linking)</isbn><accession-num>11256959</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11256959</url></related-urls></urls><custom2>1221722</custom2></record></Cite></EndNote>61. These four cysteines have reactive thiol groups, which can undergo oxidative modification like S-Nitrosylation or S-Glutathiolation during normal or pathological cellular events ADDIN EN.CITE <EndNote><Cite><Author>Gabriela M. Kuster</Author><Year>2005</Year><RecNum>6</RecNum><DisplayText>62</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1512318507″>6</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Gabriela M. Kuster, MD</author><author>David R. Pimentel, MD</author><author>Takeshi Adachi, MD, PhD</author><author>Yasuo Ido, MD, PhD</author><author>Daniel A. Brenner, MA</author><author>Richard A. Cohen, MD</author><author>Ronglih Liao, PhD</author><author>Deborah A. Siwik, PhD</author><author>Wilson S. Colucci, MD</author></authors></contributors><titles><title>Alpha-Adrenergic Receptor–Stimulated Hypertrophy in Adult Rat Ventricular Myocytes Is Mediated via Thioredoxin-1–Sensitive Oxidative Modification of Thiols on Ras</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><dates><year>2005</year></dates><urls><related-urls><url>http://www.circulationaha.or</url></related-urls></urls><electronic-resource-num>10.1161/01.CIR.0000157148.59308.F5</electronic-resource-num></record></Cite></EndNote>62. When they undergo oxidative modification, the GTP/GDP ratio is affected and changes its activities ADDIN EN.CITE <EndNote><Cite><Author>Mallis</Author><Year>2001</Year><RecNum>5</RecNum><DisplayText>61</DisplayText><record><rec-number>5</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1512316477″>5</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Mallis, R. J.</author><author>Buss, J. E.</author><author>Thomas, J. A.</author></authors></contributors><auth-address>Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, U.S.A.</auth-address><titles><title>Oxidative modification of H-ras: S-thiolation and S-nitrosylation of reactive cysteines</title><secondary-title>Biochem J</secondary-title><alt-title>The Biochemical journal</alt-title></titles><periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></periodical><alt-periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></alt-periodical><pages>145-53</pages><volume>355</volume><number>Pt 1</number><keywords><keyword>3T3 Cells</keyword><keyword>Animals</keyword><keyword>Cysteine/*metabolism</keyword><keyword>Electrophoresis, Polyacrylamide Gel</keyword><keyword>Mice</keyword><keyword>Nitroso Compounds/*metabolism</keyword><keyword>Oncogene Protein p21(ras)/chemistry/*metabolism</keyword><keyword>Oxidation-Reduction</keyword><keyword>Precipitin Tests</keyword><keyword>Sulfhydryl Compounds/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 1</date></pub-dates></dates><isbn>0264-6021 (Print) 0264-6021 (Linking)</isbn><accession-num>11256959</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11256959</url></related-urls></urls><custom2>1221722</custom2></record></Cite></EndNote>61 which mostly is activation of the cell signaling pathway. In cell cultures, H202 activated different members of MAPK superfamily and cause ERK activity to increase about 25 folds while other members like JNK and P38 activities increased in about 3-5 folds than the 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 63 and this activation was largely inhibited by an antioxidant 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 64. Inhibiting rise in H2O2 inhibited MAPK pathway activation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 65. All these emphasize on the importance of ROS in MAPK signaling. Growth factors have been known to activate MAPK pathway, this activation depends on the production ROS 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 66.ROS activating MAPK pathway have largely been reported in causing myocardial hypertrophy. The ?-Adrenoceptor causes cellular hypertrophy by increasing protein synthesis and sarcomere organization. In adult rat, ventricular myocyte hypertrophy by ? -Adrenoceptor stimulation, was through activation of MAPK signaling pathway, the activation was highly inhibited by TRX 1 (Theoredoxin-1) which is an oxidoreductase that maintains intracellular thiols in a reduced state, by so doing it prevents oxidation of RAS thiols and prevents activation of MAPK signaling. TRX 1 over expression inhibited cardiac hypertrophy and sarcomere organization in rat’s ventricular myocytes ADDIN EN.CITE <EndNote><Cite><Author>Gabriela M. Kuster</Author><Year>2005</Year><RecNum>6</RecNum><DisplayText>62</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1512318507″>6</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Gabriela M. Kuster, MD</author><author>David R. Pimentel, MD</author><author>Takeshi Adachi, MD, PhD</author><author>Yasuo Ido, MD, PhD</author><author>Daniel A. Brenner, MA</author><author>Richard A. Cohen, MD</author><author>Ronglih Liao, PhD</author><author>Deborah A. Siwik, PhD</author><author>Wilson S. Colucci, MD</author></authors></contributors><titles><title>Alpha-Adrenergic Receptor–Stimulated Hypertrophy in Adult Rat Ventricular Myocytes Is Mediated via Thioredoxin-1–Sensitive Oxidative Modification of Thiols on Ras</title><secondary-title>Circulation</secondary-title></titles><periodical><full-title>Circulation</full-title></periodical><dates><year>2005</year></dates><urls><related-urls><url>http://www.circulationaha.or</url></related-urls></urls><electronic-resource-num>10.1161/01.CIR.0000157148.59308.F5</electronic-resource-num></record></Cite></EndNote>62. Left ventricular hypertrophy due to pressure overload is also reported to be due to ROS activation of MAPK signaling, in here ROS was due o increase in the activity of NADPH oxidase ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>2002</Year><RecNum>89</RecNum><DisplayText>67</DisplayText><record><rec-number>89</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1519724848″>89</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Li, J. M.</author><author>Gall, N. P.</author><author>Grieve, D. J.</author><author>Chen, M.</author><author>Shah, A. M.</author></authors></contributors><auth-address>Department of Cardiology, Guy&apos;s King&apos;s &amp; St Thomas&apos; School of Medicine (Denmark Hill Campus), King&apos;s College London, London, United Kingdom.</auth-address><titles><title>Activation of NADPH oxidase during progression of cardiac hypertrophy to failure</title><secondary-title>Hypertension</secondary-title><alt-title>Hypertension</alt-title></titles><periodical><full-title>Hypertension</full-title><abbr-1>Hypertension</abbr-1></periodical><alt-periodical><full-title>Hypertension</full-title><abbr-1>Hypertension</abbr-1></alt-periodical><pages>477-84</pages><volume>40</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Disease Progression</keyword><keyword>Enzyme Activation</keyword><keyword>Guinea Pigs</keyword><keyword>Heart Failure/*enzymology/etiology</keyword><keyword>Hypertrophy, Left Ventricular/*enzymology/etiology</keyword><keyword>Male</keyword><keyword>Mitogen-Activated Protein Kinases/metabolism</keyword><keyword>Myocardium/enzymology</keyword><keyword>NADPH Oxidases/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Subunits</keyword><keyword>Reactive Oxygen Species/metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1524-4563 (Electronic) 0194-911X (Linking)</isbn><accession-num>12364350</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12364350</url></related-urls></urls></record></Cite></EndNote>67.Having high oxidative stress in patients with HCM and the activation of MAPK pathway in the disease pathogenesis makes oxidative stress a possible activator of MAPK pathway, which leads into development of the cardiac hypertrophy and other phenotypes in patients with HCM. There is few if any research done on the activation of MAPK by ROS as a possible mechanism that leads into expression of the phenotypes present in HCM. Further research need to be done on this pathway to widen the options for possible disease cure.2.2.2.2. PI3K- AKT- mTOR signaling pathway;This is an intracellular signaling pathway which does many of cellular functions and most importantly it controls the cell cycle, by so doing it is directly involved in cellular quiescence, cellular proliferation and even in cancers. The pathway is activated by various factors like growth factors, hormones, and cytokines. In the process of activation, the ligand binds the membranous embedded receptor tyrosine kinase (RTK) and cause receptor phosphorylation, the Insulin receptor substrate 1 (IRS1) binds the phosphorylated site and act as an anchor and activator of Phosphotidylinositol-3- kinase (PI3K), the PI3K can also bind directly on the phosphorylated receptor and becomes activated. The third mechanism in which PI3K is activated is by binding the activated RAS-GTP. The activated PI3K migrates to the inner side of the membrane and binds PIP2, which is a regular component in the cell membrane and phosphorylate it to form (Phosphatidylinositol- 3,4,5 -triphosphate) PIP3. PIP3 activate AKT, a protooncoprotein with a vast amount of substrates in its downstream. Through its action on various substrates, AKT inhibits Apoptosis and activates protein synthesis. One of the most important downstream effectors of AKT is MTOR (Mammalian target of Rapamycin), which is activated by AKT through Rheb protein. MTOR activates a translation factor S6K that binds the large ribosomal subunit and activates translation of MRNA into proteins 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 68, 69.Figure SEQ Figure * ARABIC 5; PI3K/Akt/mTOR signaling cascadeSignaling through a trans-membrane receptor activates the PI3K signaling which phosphorylate Akt and exerts its functions like promoting cell proliferation through mTOR. There are multiple feedback loops that have been shown which are currently the target for many therapies including cancer therapy 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ADDIN EN.CITE.DATA 70.PI3K/AKT pathway plays an important role in cardiac functions and diseases. It regulates different cardiac functions like metabolism, protein synthesis and inhibition of apoptosis hence cardiac adaptation ADDIN EN.CITE <EndNote><Cite><Author>Harvey</Author><Year>2011</Year><RecNum>13</RecNum><DisplayText>71</DisplayText><record><rec-number>13</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1514979867″>13</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Harvey, P. A.</author><author>Leinwand, L. A.</author></authors></contributors><auth-address>Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, USA.</auth-address><titles><title>The cell biology of disease: cellular mechanisms of cardiomyopathy</title><secondary-title>J Cell Biol</secondary-title><alt-title>The Journal of cell biology</alt-title></titles><periodical><full-title>J Cell Biol</full-title><abbr-1>The Journal of cell biology</abbr-1></periodical><alt-periodical><full-title>J Cell Biol</full-title><abbr-1>The Journal of cell biology</abbr-1></alt-periodical><pages>355-65</pages><volume>194</volume><number>3</number><keywords><keyword>Apoptosis</keyword><keyword>Cardiomyopathies/genetics/*pathology/*physiopathology</keyword><keyword>Heart/*physiopathology</keyword><keyword>Humans</keyword><keyword>Myocardium/metabolism/*pathology</keyword><keyword>Necrosis</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>Signal Transduction/genetics</keyword></keywords><dates><year>2011</year><pub-dates><date>Aug 8</date></pub-dates></dates><isbn>1540-8140 (Electronic) 0021-9525 (Linking)</isbn><accession-num>21825071</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21825071</url></related-urls></urls><custom2>3153638</custom2><electronic-resource-num>10.1083/jcb.201101100</electronic-resource-num></record></Cite></EndNote>71. MTOR exerts its action through two distinct multiprotein complexes, MTOR complex 1 (mTORC1) and MTOR complex 2 (MTORC2) ADDIN EN.CITE <EndNote><Cite><Author>Sciarretta</Author><Year>2014</Year><RecNum>18</RecNum><DisplayText>72</DisplayText><record><rec-number>18</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1514988635″>18</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Sciarretta, S.</author><author>Volpe, M.</author><author>Sadoshima, J.</author></authors></contributors><auth-address>From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ (S.S., J.S.); IRCCS Neuromed, Pozzilli, Italy (S.S., M.V.); and Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University Sapienza, Rome, Italy (M.V.).</auth-address><titles><title>Mammalian target of rapamycin signaling in cardiac physiology and disease</title><secondary-title>Circ Res</secondary-title><alt-title>Circulation research</alt-title></titles><periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></periodical><alt-periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></alt-periodical><pages>549-64</pages><volume>114</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Heart Diseases/*metabolism/pathology/*physiopathology</keyword><keyword>Humans</keyword><keyword>Myocardium/cytology/metabolism/pathology</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>TOR Serine-Threonine Kinases/*physiology</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 31</date></pub-dates></dates><isbn>1524-4571 (Electronic) 0009-7330 (Linking)</isbn><accession-num>24481845</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24481845</url></related-urls></urls><custom2>3995130</custom2><electronic-resource-num>10.1161/CIRCRESAHA.114.302022</electronic-resource-num></record></Cite></EndNote>72. MTORC1 regulates cellular functions like protein synthesis, cell growth and proliferation, cell metabolism, autophagy, and stress responses, and MTORC2 seems to regulate cell survival and polarity ADDIN EN.CITE <EndNote><Cite><Author>Sciarretta</Author><Year>2014</Year><RecNum>18</RecNum><DisplayText>72</DisplayText><record><rec-number>18</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1514988635″>18</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Sciarretta, S.</author><author>Volpe, M.</author><author>Sadoshima, J.</author></authors></contributors><auth-address>From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ (S.S., J.S.); IRCCS Neuromed, Pozzilli, Italy (S.S., M.V.); and Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University Sapienza, Rome, Italy (M.V.).</auth-address><titles><title>Mammalian target of rapamycin signaling in cardiac physiology and disease</title><secondary-title>Circ Res</secondary-title><alt-title>Circulation research</alt-title></titles><periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></periodical><alt-periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></alt-periodical><pages>549-64</pages><volume>114</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Heart Diseases/*metabolism/pathology/*physiopathology</keyword><keyword>Humans</keyword><keyword>Myocardium/cytology/metabolism/pathology</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>TOR Serine-Threonine Kinases/*physiology</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 31</date></pub-dates></dates><isbn>1524-4571 (Electronic) 0009-7330 (Linking)</isbn><accession-num>24481845</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24481845</url></related-urls></urls><custom2>3995130</custom2><electronic-resource-num>10.1161/CIRCRESAHA.114.302022</electronic-resource-num></record></Cite></EndNote>72. mTor pathway have been reported to participate in the pathogenesis of HCM. In mutant mice with Ptpn 11 mutation having Leopards syndrome and concurrent HCM, the Akt/mTor pathway was hyper activated in the heart muscles. Other pathways like MAPK pathways were also activated. Upon a short-term treatment with Rapamycin, all the cardiac phenotypes disappeared which showed the potential involvement of Akt/mTor pathway in inducing HCM phenotypes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 73. Rapamycin is an inhibitor of Akt/mTor pathway, which acts by destabilizing mTor-Raptor complex 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PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMjwveWVhcj48cHViLWRhdGVzPjxkYXRlPkphbiAxPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MTUyMi0xNTM5IChFbGVjdHJvbmljKSYjeEQ7MDM2My02MTM1IChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT4yMjA1ODE1MzwvYWNjZXNzaW9uLW51bT48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL3d3dy5uY2JpLm5sbS5uaWguZ292L3B1Ym1lZC8yMjA1ODE1MzwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTE1Mi9hanBoZWFydC4wMDY2NS4yMDExPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn== ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 74, 75. While all these reports are from mutant mice, a report of a patient having Noonan syndrome with multiple lentigines (NSML) with a rapid progressive HCM, showed above level activities of Akt/mTor signaling where the cardiac functions were also improved by a Rapamycin analogue 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 59. Mutation in the PTEN caused deregulation of PI3K/Akt/mTor pathway that ended up with HCM 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 76. PTEN is PIP3 inhibitor as it prevents phosphorylation of PIP2 ADDIN EN.CITE <EndNote><Cite><Author>Leslie</Author><Year>2002</Year><RecNum>26</RecNum><DisplayText>77</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1514991404″>26</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Leslie, N. R.</author><author>Downes, C. P.</author></authors></contributors><auth-address>Division of Cell Signalling, School of Life Sciences, Medical Sciences Institute, University of Dundee, DD1 5EH Scotland, Dundee, UK. [email protected]</auth-address><titles><title>PTEN: The down side of PI 3-kinase signalling</title><secondary-title>Cell Signal</secondary-title><alt-title>Cellular signalling</alt-title></titles><periodical><full-title>Cell Signal</full-title><abbr-1>Cellular signalling</abbr-1></periodical><alt-periodical><full-title>Cell Signal</full-title><abbr-1>Cellular signalling</abbr-1></alt-periodical><pages>285-95</pages><volume>14</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Inositol Phosphates/chemistry/metabolism</keyword><keyword>Models, Biological</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Phosphatidylinositol 3-Kinases/*antagonists &amp; inhibitors</keyword><keyword>Phosphoric Monoester Hydrolases/chemistry/*metabolism</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>Signal Transduction</keyword><keyword>Tumor Suppressor Proteins/chemistry/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0898-6568 (Print) 0898-6568 (Linking)</isbn><accession-num>11858936</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11858936</url></related-urls></urls></record></Cite></EndNote>77.Cardiac hypertrophy due to other causes like pressure overload depends largely on the activation of Akt/mTor signaling pathway as well. In aortic banded mice, there was highly activated Akt/ mTor pathway components, S6K1, S6 phosphorylation had increased and elF4E was up regulated. Rapamycin reduced cardiac hypertrophy and improved the left ventricular function by attenuating S6 and 4E-BP1 phosphorylation therefore reduced the S6K and elF4E activities in both acute and chronic cases <EndNote><Cite><Author>McMullen</Author><Year>2004</Year><RecNum>20</RecNum><DisplayText>[78-80]</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1514989124">20</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McMullen, J. R.</author><author>Sherwood, M. C.</author><author>Tarnavski, O.</author><author>Zhang, L.</author><author>Dorfman, A. L.</author><author>Shioi, T.</author><author>Izumo, S.</author></authors></contributors><auth-address>Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, Mass 02215, USA. jmcmulle@bidmc.harvard.edu</auth-address><titles><title>Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>3050-5</pages><volume>109</volume><number>24</number><keywords><keyword>Adaptation, Physiological</keyword><keyword>Animals</keyword><keyword>Aorta</keyword><keyword>Aortic Diseases/complications</keyword><keyword>Cardiomegaly/*drug therapy/etiology</keyword><keyword>Cell Size/drug effects</keyword><keyword>Constriction, Pathologic/complications</keyword><keyword>Drug Evaluation, Preclinical</keyword><keyword>Gene Expression Regulation/drug effects</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Myocytes, Cardiac/pathology</keyword><keyword>Organ Size/drug effects</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinases/*drug effects/physiology</keyword><keyword>Protein Processing, Post-Translational/drug effects</keyword><keyword>Ribosomal Protein S6/metabolism</keyword><keyword>Sirolimus/pharmacology/*therapeutic use</keyword><keyword>Stroke Volume/drug effects</keyword><keyword>TOR Serine-Threonine Kinases</keyword></keywords><dates><year>2004</year><pub-dates><date>Jun 22</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>15184287</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15184287</url></related-urls></urls><electronic-resource-num>10.1161/01.CIR.0000130641.08705.45</electronic-resource-num></record></Cite><Cite><Author>Shioi</Author><Year>2003</Year><RecNum>16</RecNum><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1514984186">16</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shioi, T.</author><author>McMullen, J. R.</author><author>Tarnavski, O.</author><author>Converso, K.</author><author>Sherwood, M. C.</author><author>Manning, W. J.</author><author>Izumo, S.</author></authors></contributors><auth-address>Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, Mass 02215, USA.</auth-address><titles><title>Rapamycin attenuates load-induced cardiac hypertrophy in mice</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>1664-70</pages><volume>107</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Aorta</keyword><keyword>Cardiomegaly/*etiology/metabolism/pathology</keyword><keyword>Constriction</keyword><keyword>Fetus/drug effects/metabolism</keyword><keyword>Gene Expression Regulation</keyword><keyword>Glycogen Synthase Kinase 3/metabolism</keyword><keyword>Glycogen Synthase Kinase 3 beta</keyword><keyword>Heart/physiopathology</keyword><keyword>Hemodynamics/drug effects</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinase 8</keyword><keyword>Mitogen-Activated Protein Kinases/metabolism</keyword><keyword>Myocardium/metabolism/pathology</keyword><keyword>Myocytes, Cardiac/pathology</keyword><keyword>Organ Size</keyword><keyword>Phosphorylation</keyword><keyword>*Protein Kinase Inhibitors</keyword><keyword>Protein Kinases/physiology</keyword><keyword>RNA, Messenger/biosynthesis</keyword><keyword>Ribosomal Protein S6/metabolism</keyword><keyword>Ribosomal Protein S6 Kinases, 70-kDa/metabolism</keyword><keyword>Sirolimus/*pharmacology</keyword><keyword>TOR Serine-Threonine Kinases</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr 1</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>12668503</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12668503</url></related-urls></urls><electronic-resource-num>10.1161/01.CIR.0000057979.36322.88</electronic-resource-num></record></Cite><Cite><Author>Gao</Author><Year>2006</Year><RecNum>91</RecNum><record><rec-number>91</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1519804119">91</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gao, X. M.</author><author>Wong, G.</author><author>Wang, B.</author><author>Kiriazis, H.</author><author>Moore, X. L.</author><author>Su, Y. D.</author><author>Dart, A.</author><author>Du, X. J.</author></authors></contributors><auth-address>Experimental Cardiology Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia. xiaoming.gao@baker.edu.au</auth-address><titles><title>Inhibition of mTOR reduces chronic pressure-overload cardiac hypertrophy and fibrosis</title><secondary-title>J Hypertens</secondary-title><alt-title>Journal of hypertension</alt-title></titles><periodical><full-title>J Hypertens</full-title><abbr-1>Journal of hypertension</abbr-1></periodical><alt-periodical><full-title>J Hypertens</full-title><abbr-1>Journal of hypertension</abbr-1></alt-periodical><pages>1663-70</pages><volume>24</volume><number>8</number><keywords><keyword>Analysis of Variance</keyword><keyword>Animals</keyword><keyword>Atrial Natriuretic Factor/drug effects/metabolism</keyword><keyword>*Blood Pressure</keyword><keyword>Chronic Disease</keyword><keyword>Disease Models, Animal</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Eukaryotic Initiation Factor-4E/drug effects/metabolism</keyword><keyword>Fibrosis</keyword><keyword>Heart Rate</keyword><keyword>Hypertrophy, Left Ventricular/*metabolism/*physiopathology</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinase 3/drug effects/metabolism</keyword><keyword>Myosin Heavy Chains/drug effects/metabolism</keyword><keyword>Phosphatidylinositol 3-Kinases/drug effects/metabolism</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Kinases/drug effects/*metabolism</keyword><keyword>Ribosomal Protein S6/drug effects/metabolism</keyword><keyword>STAT3 Transcription Factor/drug effects/metabolism</keyword><keyword>Sarcoplasmic Reticulum Calcium-Transporting ATPases/drug effects/metabolism</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>Sirolimus/pharmacology</keyword><keyword>Stroke Volume</keyword><keyword>TOR Serine-Threonine Kinases</keyword></keywords><dates><year>2006</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0263-6352 (Print)&#xD;0263-6352 (Linking)</isbn><accession-num>16877971</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16877971</url></related-urls></urls><electronic-resource-num>10.1097/01.hjh.0000239304.01496.83</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>McMullen</Author><Year>2004</Year><RecNum>20</RecNum><DisplayText>[78-80]</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1514989124">20</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McMullen, J. R.</author><author>Sherwood, M. C.</author><author>Tarnavski, O.</author><author>Zhang, L.</author><author>Dorfman, A. L.</author><author>Shioi, T.</author><author>Izumo, S.</author></authors></contributors><auth-address>Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, Mass 02215, USA. jmcmulle@bidmc.harvard.edu</auth-address><titles><title>Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>3050-5</pages><volume>109</volume><number>24</number><keywords><keyword>Adaptation, Physiological</keyword><keyword>Animals</keyword><keyword>Aorta</keyword><keyword>Aortic Diseases/complications</keyword><keyword>Cardiomegaly/*drug therapy/etiology</keyword><keyword>Cell Size/drug effects</keyword><keyword>Constriction, Pathologic/complications</keyword><keyword>Drug Evaluation, Preclinical</keyword><keyword>Gene Expression Regulation/drug effects</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Myocytes, Cardiac/pathology</keyword><keyword>Organ Size/drug effects</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinases/*drug effects/physiology</keyword><keyword>Protein Processing, Post-Translational/drug effects</keyword><keyword>Ribosomal Protein S6/metabolism</keyword><keyword>Sirolimus/pharmacology/*therapeutic use</keyword><keyword>Stroke Volume/drug effects</keyword><keyword>TOR Serine-Threonine Kinases</keyword></keywords><dates><year>2004</year><pub-dates><date>Jun 22</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>15184287</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15184287</url></related-urls></urls><electronic-resource-num>10.1161/01.CIR.0000130641.08705.45</electronic-resource-num></record></Cite><Cite><Author>Shioi</Author><Year>2003</Year><RecNum>16</RecNum><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1514984186">16</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shioi, T.</author><author>McMullen, J. R.</author><author>Tarnavski, O.</author><author>Converso, K.</author><author>Sherwood, M. C.</author><author>Manning, W. J.</author><author>Izumo, S.</author></authors></contributors><auth-address>Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, Mass 02215, USA.</auth-address><titles><title>Rapamycin attenuates load-induced cardiac hypertrophy in mice</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>1664-70</pages><volume>107</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Aorta</keyword><keyword>Cardiomegaly/*etiology/metabolism/pathology</keyword><keyword>Constriction</keyword><keyword>Fetus/drug effects/metabolism</keyword><keyword>Gene Expression Regulation</keyword><keyword>Glycogen Synthase Kinase 3/metabolism</keyword><keyword>Glycogen Synthase Kinase 3 beta</keyword><keyword>Heart/physiopathology</keyword><keyword>Hemodynamics/drug effects</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinase 8</keyword><keyword>Mitogen-Activated Protein Kinases/metabolism</keyword><keyword>Myocardium/metabolism/pathology</keyword><keyword>Myocytes, Cardiac/pathology</keyword><keyword>Organ Size</keyword><keyword>Phosphorylation</keyword><keyword>*Protein Kinase Inhibitors</keyword><keyword>Protein Kinases/physiology</keyword><keyword>RNA, Messenger/biosynthesis</keyword><keyword>Ribosomal Protein S6/metabolism</keyword><keyword>Ribosomal Protein S6 Kinases, 70-kDa/metabolism</keyword><keyword>Sirolimus/*pharmacology</keyword><keyword>TOR Serine-Threonine Kinases</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr 1</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>12668503</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12668503</url></related-urls></urls><electronic-resource-num>10.1161/01.CIR.0000057979.36322.88</electronic-resource-num></record></Cite><Cite><Author>Gao</Author><Year>2006</Year><RecNum>91</RecNum><record><rec-number>91</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1519804119">91</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gao, X. M.</author><author>Wong, G.</author><author>Wang, B.</author><author>Kiriazis, H.</author><author>Moore, X. L.</author><author>Su, Y. D.</author><author>Dart, A.</author><author>Du, X. J.</author></authors></contributors><auth-address>Experimental Cardiology Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia. xiaoming.gao@baker.edu.au</auth-address><titles><title>Inhibition of mTOR reduces chronic pressure-overload cardiac hypertrophy and fibrosis</title><secondary-title>J Hypertens</secondary-title><alt-title>Journal of hypertension</alt-title></titles><periodical><full-title>J Hypertens</full-title><abbr-1>Journal of hypertension</abbr-1></periodical><alt-periodical><full-title>J Hypertens</full-title><abbr-1>Journal of hypertension</abbr-1></alt-periodical><pages>1663-70</pages><volume>24</volume><number>8</number><keywords><keyword>Analysis of Variance</keyword><keyword>Animals</keyword><keyword>Atrial Natriuretic Factor/drug effects/metabolism</keyword><keyword>*Blood Pressure</keyword><keyword>Chronic Disease</keyword><keyword>Disease Models, Animal</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Eukaryotic Initiation Factor-4E/drug effects/metabolism</keyword><keyword>Fibrosis</keyword><keyword>Heart Rate</keyword><keyword>Hypertrophy, Left Ventricular/*metabolism/*physiopathology</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinase 3/drug effects/metabolism</keyword><keyword>Myosin Heavy Chains/drug effects/metabolism</keyword><keyword>Phosphatidylinositol 3-Kinases/drug effects/metabolism</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Kinases/drug effects/*metabolism</keyword><keyword>Ribosomal Protein S6/drug effects/metabolism</keyword><keyword>STAT3 Transcription Factor/drug effects/metabolism</keyword><keyword>Sarcoplasmic Reticulum Calcium-Transporting ATPases/drug effects/metabolism</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>Sirolimus/pharmacology</keyword><keyword>Stroke Volume</keyword><keyword>TOR Serine-Threonine Kinases</keyword></keywords><dates><year>2006</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0263-6352 (Print)&#xD;0263-6352 (Linking)</isbn><accession-num>16877971</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16877971</url></related-urls></urls><electronic-resource-num>10.1097/01.hjh.0000239304.01496.83</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 78-80. 4E-BP1 is a translational repressor. In its unphosphorylated state, it binds eIF4E and prevents its interaction with 5′- end of MRNA and prevents translational initiation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 81.ROS (oxidative stress) has been reported to play a role in cardiac hypertrophy through activation of Akt pathway, one of the mechanism involved was through activation of Rac 1, a GTPase binding protein 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 82. A Nox4/Nox1 inhibitor, antioxidant that reduced prevented cardiac hypertrophy and remodeling in the mice models 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 81. In the male wister rats experiment, celecoxib acted as a potent antioxidant by inhibiting gene transcription of multiple antioxidants and by so doing there was also inhibition of Akt/mTor signaling and regression of cardiac hypertrophy in experimental animals. All these support the role of oxidative stress in cardiac hypertrophy when Akt/mTor signaling is activated. Despite the fact that, HCM involves increase in oxidative stress and activation of Akt/mTor signaling pathway in some case, these two facts have been described separately and non of the experiment have ever related the possibility of rising oxidative stress being the cause of Akt/mTor signaling activation in patients with HCM. Further experiments are needed in this area in older to solve the existing puzzle of the cure for HCM. 2.2.2.3. Ca2+/ Calcineurin/ NF-AT signaling pathway;NF-AT (Nuclear factor of activated T-cell) is a transcription factor that normally exists in the cytoplasm of the cell in its inactive form when the cell is not activated. It is kept inactive by the phosphorylation in its serine and threonine residues, by so doing; they block the NF-AT nuclear localization signal. The calcium binding protein, Calmodulin and calcium dependent phosphatase, calcineurin are responsible for the activation of NF-AT. When the ligand binds the calcium release activated channel, it opens and allows the extracellular calcium to enter the cytoplasm and binds the Calmodulin. Calmodulin undergo conformational change and acts on other cellular proteins one them being Calcineurin. Once bound to calmodulin it becomes active and activates NF-AT by dephosphorylating it. The activated NF-AT enters the nucleus and binds to the promoters of many inducible genes and initiates their transcription 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 83, 84. Various stimuli have been said to increase intracellular Ca2+ like Angiotensin II, phenylephrine and 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 85, and even more interesting some of them are already studied extensively in the pathogenesis of cardiac 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 86, 87. Figure SEQ Figure * ARABIC 6; calcineurin/ NF-AT signaling pathway Schematic diagram shows calcinerin activation by increased intracellular calcium which then cause NFAT dephosphorylation and nuclear. Some calcinerin inhibitors are shown in the cytoplasm which antagonizes its nuclear translocationor even facilitating its egress. While green lines denote activation events, the red lines denote its inhibitory events 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 88. Calcineurin/ NF-AT signaling have been discovered to participate in the development of HCM. This was proved so in the transgenic mutant mice with dominant negative mutant for P38 gene that developed HCM; this was due to the fact that, P38 regulates NF-AT signaling by inhibiting its dephosphorylation. In these mice models with negative P38, NF-AT was hyperactivated and developed HCM 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 89. In patients with hypertrophic obstructive cardiomyopathy, calcineurin activities were highly increased due to proteolysis of the calcineurin autoinhibitory domain; this led to increased NF-AT activities in these patients and suggests its involvement in the pathogenesis of the disease 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 90. NF-AT signaling have also been reported in other cardiac hypertrophies which are not HCM, experiments on laboratory animals with cardiac hypertrophy from various causes like aortic banding, hypertension, carnitine deficiency demonstrated increased activity above range of this pathway <EndNote><Cite><Author>Molkentin</Author><Year>1998</Year><RecNum>44</RecNum><DisplayText>[85, 91-93]</DisplayText><record><rec-number>44</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413119">44</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Molkentin, J. D.</author><author>Lu, J. R.</author><author>Antos, C. L.</author><author>Markham, B.</author><author>Richardson, J.</author><author>Robbins, J.</author><author>Grant, S. R.</author><author>Olson, E. N.</author></authors></contributors><auth-address>Department of Molecular Biology and Oncology, The University of Texas Southwestern Medical Center at Dallas, 75225-9148, USA.</auth-address><titles><title>A calcineurin-dependent transcriptional pathway for cardiac hypertrophy</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>215-28</pages><volume>93</volume><number>2</number><keywords><keyword>Angiotensin II/pharmacology</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Atrial Natriuretic Factor/genetics</keyword><keyword>Calcineurin/genetics/*physiology</keyword><keyword>Cardiomegaly/enzymology/*genetics/prevention &amp; control</keyword><keyword>Cell Nucleus/metabolism</keyword><keyword>DNA-Binding Proteins/metabolism</keyword><keyword>GATA4 Transcription Factor</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Myocardium/metabolism/*pathology</keyword><keyword>NFATC Transcription Factors</keyword><keyword>Natriuretic Peptide, Brain</keyword><keyword>*Nuclear Proteins</keyword><keyword>Phenylephrine/pharmacology</keyword><keyword>Promoter Regions, Genetic/genetics</keyword><keyword>Rats</keyword><keyword>Recombinant Fusion Proteins</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Transcription Factors/metabolism</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation/*physiology</keyword><keyword>Zinc Fingers</keyword></keywords><dates><year>1998</year><pub-dates><date>Apr 17</date></pub-dates></dates><isbn>0092-8674 (Print)&#xD;0092-8674 (Linking)</isbn><accession-num>9568714</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9568714</url></related-urls></urls><custom2>4459646</custom2></record></Cite><Cite><Author>Lim</Author><Year>2000</Year><RecNum>45</RecNum><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413418">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lim, H. W.</author><author>De Windt, L. J.</author><author>Steinberg, L.</author><author>Taigen, T.</author><author>Witt, S. A.</author><author>Kimball, T. R.</author><author>Molkentin, J. D.</author></authors></contributors><auth-address>Department of Pediatrics, Children&apos;s Hospital Medical Center, University of Cincinnati, Ohio, USA.</auth-address><titles><title>Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>2431-7</pages><volume>101</volume><number>20</number><keywords><keyword>Animals</keyword><keyword>Calcineurin/metabolism/*physiology</keyword><keyword>Calcineurin Inhibitors</keyword><keyword>Cardiomegaly/*etiology/metabolism/*physiopathology/prevention &amp; control</keyword><keyword>Cyclosporine/pharmacology</keyword><keyword>Disease Progression</keyword><keyword>Female</keyword><keyword>Hypertension/*complications</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword></keywords><dates><year>2000</year><pub-dates><date>May 23</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>10821822</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10821822</url></related-urls></urls></record></Cite><Cite><Author>Shimoyama</Author><Year>1999</Year><RecNum>46</RecNum><record><rec-number>46</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413511">46</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shimoyama, M.</author><author>Hayashi, D.</author><author>Takimoto, E.</author><author>Zou, Y.</author><author>Oka, T.</author><author>Uozumi, H.</author><author>Kudoh, S.</author><author>Shibasaki, F.</author><author>Yazaki, Y.</author><author>Nagai, R.</author><author>Komuro, I.</author></authors></contributors><auth-address>Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, and the Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.</auth-address><titles><title>Calcineurin plays a critical role in pressure overload-induced cardiac hypertrophy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>2449-54</pages><volume>100</volume><number>24</number><keywords><keyword>Animals</keyword><keyword>Aorta, Abdominal/physiopathology/surgery</keyword><keyword>Atrial Natriuretic Factor/genetics</keyword><keyword>*Blood Volume</keyword><keyword>Body Weight</keyword><keyword>Calcineurin/genetics/*metabolism</keyword><keyword>Calcineurin Inhibitors</keyword><keyword>Cardiomegaly/diagnostic imaging/*metabolism/*prevention &amp; control</keyword><keyword>Constriction, Pathologic</keyword><keyword>Disease Models, Animal</keyword><keyword>Echocardiography</keyword><keyword>Fibrosis</keyword><keyword>Gene Expression/physiology</keyword><keyword>Genes, Immediate-Early/physiology</keyword><keyword>Heart Rate/drug effects</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Male</keyword><keyword>Myocardium/pathology</keyword><keyword>Proto-Oncogene Proteins c-fos/genetics</keyword><keyword>Proto-Oncogene Proteins c-jun/genetics</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Tacrolimus/pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>Dec 14</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>10595959</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10595959</url></related-urls></urls></record></Cite><Cite><Author>Zou</Author><Year>2001</Year><RecNum>49</RecNum><record><rec-number>49</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413861">49</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zou, Y.</author><author>Hiroi, Y.</author><author>Uozumi, H.</author><author>Takimoto, E.</author><author>Toko, H.</author><author>Zhu, W.</author><author>Kudoh, S.</author><author>Mizukami, M.</author><author>Shimoyama, M.</author><author>Shibasaki, F.</author><author>Nagai, R.</author><author>Yazaki, Y.</author><author>Komuro, I.</author></authors></contributors><auth-address>Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba.</auth-address><titles><title>Calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>97-101</pages><volume>104</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Aorta, Abdominal/pathology</keyword><keyword>Blood Pressure</keyword><keyword>Body Weight</keyword><keyword>Calcineurin/genetics/*metabolism</keyword><keyword>Cardiomegaly/*etiology/pathology/*physiopathology</keyword><keyword>Catalysis</keyword><keyword>Constriction, Pathologic</keyword><keyword>Disease Models, Animal</keyword><keyword>Disease Progression</keyword><keyword>Echocardiography</keyword><keyword>Enzyme Activation/genetics</keyword><keyword>Fibrosis/pathology</keyword><keyword>Gene Expression</keyword><keyword>Genes, Dominant</keyword><keyword>Genes, Immediate-Early</keyword><keyword>Hypertension/*complications/*physiopathology</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Mitogen-Activated Protein Kinases/metabolism</keyword><keyword>Mutagenesis, Site-Directed</keyword><keyword>Organ Size</keyword><keyword>Organ Specificity/genetics</keyword></keywords><dates><year>2001</year><pub-dates><date>Jul 3</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>11435345</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11435345</url></related-urls></urls></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Molkentin</Author><Year>1998</Year><RecNum>44</RecNum><DisplayText>[85, 91-93]</DisplayText><record><rec-number>44</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413119">44</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Molkentin, J. D.</author><author>Lu, J. R.</author><author>Antos, C. L.</author><author>Markham, B.</author><author>Richardson, J.</author><author>Robbins, J.</author><author>Grant, S. R.</author><author>Olson, E. N.</author></authors></contributors><auth-address>Department of Molecular Biology and Oncology, The University of Texas Southwestern Medical Center at Dallas, 75225-9148, USA.</auth-address><titles><title>A calcineurin-dependent transcriptional pathway for cardiac hypertrophy</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>215-28</pages><volume>93</volume><number>2</number><keywords><keyword>Angiotensin II/pharmacology</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Atrial Natriuretic Factor/genetics</keyword><keyword>Calcineurin/genetics/*physiology</keyword><keyword>Cardiomegaly/enzymology/*genetics/prevention &amp; control</keyword><keyword>Cell Nucleus/metabolism</keyword><keyword>DNA-Binding Proteins/metabolism</keyword><keyword>GATA4 Transcription Factor</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Myocardium/metabolism/*pathology</keyword><keyword>NFATC Transcription Factors</keyword><keyword>Natriuretic Peptide, Brain</keyword><keyword>*Nuclear Proteins</keyword><keyword>Phenylephrine/pharmacology</keyword><keyword>Promoter Regions, Genetic/genetics</keyword><keyword>Rats</keyword><keyword>Recombinant Fusion Proteins</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Transcription Factors/metabolism</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation/*physiology</keyword><keyword>Zinc Fingers</keyword></keywords><dates><year>1998</year><pub-dates><date>Apr 17</date></pub-dates></dates><isbn>0092-8674 (Print)&#xD;0092-8674 (Linking)</isbn><accession-num>9568714</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9568714</url></related-urls></urls><custom2>4459646</custom2></record></Cite><Cite><Author>Lim</Author><Year>2000</Year><RecNum>45</RecNum><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413418">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lim, H. W.</author><author>De Windt, L. J.</author><author>Steinberg, L.</author><author>Taigen, T.</author><author>Witt, S. A.</author><author>Kimball, T. R.</author><author>Molkentin, J. D.</author></authors></contributors><auth-address>Department of Pediatrics, Children&apos;s Hospital Medical Center, University of Cincinnati, Ohio, USA.</auth-address><titles><title>Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>2431-7</pages><volume>101</volume><number>20</number><keywords><keyword>Animals</keyword><keyword>Calcineurin/metabolism/*physiology</keyword><keyword>Calcineurin Inhibitors</keyword><keyword>Cardiomegaly/*etiology/metabolism/*physiopathology/prevention &amp; control</keyword><keyword>Cyclosporine/pharmacology</keyword><keyword>Disease Progression</keyword><keyword>Female</keyword><keyword>Hypertension/*complications</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword></keywords><dates><year>2000</year><pub-dates><date>May 23</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>10821822</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10821822</url></related-urls></urls></record></Cite><Cite><Author>Shimoyama</Author><Year>1999</Year><RecNum>46</RecNum><record><rec-number>46</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413511">46</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shimoyama, M.</author><author>Hayashi, D.</author><author>Takimoto, E.</author><author>Zou, Y.</author><author>Oka, T.</author><author>Uozumi, H.</author><author>Kudoh, S.</author><author>Shibasaki, F.</author><author>Yazaki, Y.</author><author>Nagai, R.</author><author>Komuro, I.</author></authors></contributors><auth-address>Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, and the Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.</auth-address><titles><title>Calcineurin plays a critical role in pressure overload-induced cardiac hypertrophy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>2449-54</pages><volume>100</volume><number>24</number><keywords><keyword>Animals</keyword><keyword>Aorta, Abdominal/physiopathology/surgery</keyword><keyword>Atrial Natriuretic Factor/genetics</keyword><keyword>*Blood Volume</keyword><keyword>Body Weight</keyword><keyword>Calcineurin/genetics/*metabolism</keyword><keyword>Calcineurin Inhibitors</keyword><keyword>Cardiomegaly/diagnostic imaging/*metabolism/*prevention &amp; control</keyword><keyword>Constriction, Pathologic</keyword><keyword>Disease Models, Animal</keyword><keyword>Echocardiography</keyword><keyword>Fibrosis</keyword><keyword>Gene Expression/physiology</keyword><keyword>Genes, Immediate-Early/physiology</keyword><keyword>Heart Rate/drug effects</keyword><keyword>Immunosuppressive Agents/pharmacology</keyword><keyword>Male</keyword><keyword>Myocardium/pathology</keyword><keyword>Proto-Oncogene Proteins c-fos/genetics</keyword><keyword>Proto-Oncogene Proteins c-jun/genetics</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Tacrolimus/pharmacology</keyword></keywords><dates><year>1999</year><pub-dates><date>Dec 14</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>10595959</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10595959</url></related-urls></urls></record></Cite><Cite><Author>Zou</Author><Year>2001</Year><RecNum>49</RecNum><record><rec-number>49</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515413861">49</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zou, Y.</author><author>Hiroi, Y.</author><author>Uozumi, H.</author><author>Takimoto, E.</author><author>Toko, H.</author><author>Zhu, W.</author><author>Kudoh, S.</author><author>Mizukami, M.</author><author>Shimoyama, M.</author><author>Shibasaki, F.</author><author>Nagai, R.</author><author>Yazaki, Y.</author><author>Komuro, I.</author></authors></contributors><auth-address>Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba.</auth-address><titles><title>Calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>97-101</pages><volume>104</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Aorta, Abdominal/pathology</keyword><keyword>Blood Pressure</keyword><keyword>Body Weight</keyword><keyword>Calcineurin/genetics/*metabolism</keyword><keyword>Cardiomegaly/*etiology/pathology/*physiopathology</keyword><keyword>Catalysis</keyword><keyword>Constriction, Pathologic</keyword><keyword>Disease Models, Animal</keyword><keyword>Disease Progression</keyword><keyword>Echocardiography</keyword><keyword>Enzyme Activation/genetics</keyword><keyword>Fibrosis/pathology</keyword><keyword>Gene Expression</keyword><keyword>Genes, Dominant</keyword><keyword>Genes, Immediate-Early</keyword><keyword>Hypertension/*complications/*physiopathology</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Mitogen-Activated Protein Kinases/metabolism</keyword><keyword>Mutagenesis, Site-Directed</keyword><keyword>Organ Size</keyword><keyword>Organ Specificity/genetics</keyword></keywords><dates><year>2001</year><pub-dates><date>Jul 3</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>11435345</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11435345</url></related-urls></urls></record></Cite></EndNote> ADDIN EN.CITE.DATA 85, 91-93. Even physiologic cardiac hypertrophy do activate calcineurin pathway ADDIN EN.CITE <EndNote><Cite><Author>Eto</Author><Year>2000</Year><RecNum>47</RecNum><DisplayText>94</DisplayText><record><rec-number>47</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1515413670″>47</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Eto, Y.</author><author>Yonekura, K.</author><author>Sonoda, M.</author><author>Arai, N.</author><author>Sata, M.</author><author>Sugiura, S.</author><author>Takenaka, K.</author><author>Gualberto, A.</author><author>Hixon, M. L.</author><author>Wagner, M. W.</author><author>Aoyagi, T.</author></authors></contributors><auth-address>Department of Cardiovascular Medicine, University of Tokyo, Japan.</auth-address><titles><title>Calcineurin is activated in rat hearts with physiological left ventricular hypertrophy induced by voluntary exercise training</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>2134-7</pages><volume>101</volume><number>18</number><keywords><keyword>Animals</keyword><keyword>Calcineurin/*physiology</keyword><keyword>Hypertrophy, Left Ventricular/*metabolism/physiopathology</keyword><keyword>Physical Conditioning, Animal/*physiology</keyword><keyword>Rats</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2000</year><pub-dates><date>May 9</date></pub-dates></dates><isbn>1524-4539 (Electronic) 0009-7322 (Linking)</isbn><accession-num>10801751</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10801751</url></related-urls></urls></record></Cite></EndNote>94. Calcineurin inhibitors like cyclosporine A and FK506, which prevent calcineurin’s ability to activate NF-AT transcription factors have proved success in treating cardiac hypertrophy in most experimental animal models 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 84, 85, even inhibition by Adenovirus expressing calcineurin inhibitory domain of AKAP79 demonstrated the same results 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 95. MAPK pathway have been reported to associate with NF-AT pathway in causing cardiac hypertrophy in a mechanism not well 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 84, the mechanism could be in part due to the ability of MAPKs to increase intracellular 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 85. The relationship of oxidative stress to this pathway is largely due to its interaction with MAPK/ ERK signaling pathway which is largely affected by oxidative stress as explained above. PICOT (PKC- Interacting cousin of thioredoxin) which is a protein kinase C inhibitor has amino terminal thioredoxin homology. While theoredoxin cause regression of cardiac hypertrophy by reducing oxidative 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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZW9uZzwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJlY051bT41MjwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bOTZdPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjUyPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZGVyZmV0MHprOXd4c3JldHAwOXB6d3hyeDUwZGZ2eGFyNTkyIiB0aW1lc3RhbXA9IjE1MTU1ODA4MzUiPjUyPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5KZW9uZywgRC48L2F1dGhvcj48YXV0aG9yPkNoYSwgSC48L2F1dGhvcj48YXV0aG9yPktpbSwgRS48L2F1dGhvcj48YXV0aG9yPkthbmcsIE0uPC9hdXRob3I+PGF1dGhvcj5ZYW5nLCBELiBLLjwvYXV0aG9yPjxhdXRob3I+S2ltLCBKLiBNLjwvYXV0aG9yPjxhdXRob3I+WW9vbiwgUC4gTy48L2F1dGhvcj48YXV0aG9yPk9oLCBKLiBHLjwvYXV0aG9yPjxhdXRob3I+QmVybmVja2VyLCBPLiBZLjwvYXV0aG9yPjxhdXRob3I+U2FrYXRhLCBTLjwvYXV0aG9yPjxhdXRob3I+TGUsIFQuIFQuPC9hdXRob3I+PGF1dGhvcj5DdWksIEwuPC9hdXRob3I+PGF1dGhvcj5MZWUsIFkuIEguPC9hdXRob3I+PGF1dGhvcj5LaW0sIEQuIEguPC9hdXRob3I+PGF1dGhvcj5Xb28sIFMuIEguPC9hdXRob3I+PGF1dGhvcj5MaWFvLCBSLjwvYXV0aG9yPjxhdXRob3I+SGFqamFyLCBSLiBKLjwvYXV0aG9yPjxhdXRob3I+UGFyaywgVy4gSi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9mIExpZmUgU2NpZW5jZSwgR2xvYmFsIFJlc2VhcmNoIExhYm9yYXRvcnkgb24gQ2FyZGlvdmFzY3VsYXIgR2VuZSBUaGVyYXB5LCBHd2FuZ2p1IEluc3RpdHV0ZSBvZiBTY2llbmNlIGFuZCBUZWNobm9sb2d5LCBLb3JlYS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5QSUNPVCBpbmhpYml0cyBjYXJkaWFjIGh5cGVydHJvcGh5IGFuZCBlbmhhbmNlcyB2ZW50cmljdWxhciBmdW5jdGlvbiBhbmQgY2FyZGlvbXlvY3l0ZSBjb250cmFjdGlsaXR5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNpcmMgUmVzPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5DaXJjdWxhdGlvbiByZXNlYXJjaDwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNpcmMgUmVzPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2lyY3VsYXRpb24gcmVzZWFyY2g8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNpcmMgUmVzPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2lyY3VsYXRpb24gcmVzZWFyY2g8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4zMDctMTQ8L3BhZ2VzPjx2b2x1bWU+OTk8L3ZvbHVtZT48bnVtYmVyPjM8L251bWJlcj48a2V5d29yZHM+PGtleXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5BbmltYWxzLCBOZXdib3JuPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb21lZ2FseS8qcHJldmVudGlvbiAmYW1wOyBjb250cm9sPC9rZXl3b3JkPjxrZXl3b3JkPkNhcnJpZXIgUHJvdGVpbnMvZ2VuZXRpY3MvKnBoeXNpb2xvZ3kvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGxzLCBDdWx0dXJlZDwva2V5d29yZD48a2V5d29yZD5Fbnp5bWUgSW5oaWJpdG9ycy9waGFybWFjb2xvZ3kvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3JkPkdlbmV0aWMgVGhlcmFweTwva2V5d29yZD48a2V5d29yZD5NaWNlPC9rZXl3b3JkPjxrZXl3b3JkPk1pY2UsIFRyYW5zZ2VuaWM8L2tleXdvcmQ+PGtleXdvcmQ+TXlvY2FyZGlhbCBDb250cmFjdGlvbjwva2V5d29yZD48a2V5d29yZD5NeW9jeXRlcywgQ2FyZGlhYy9jeXRvbG9neTwva2V5d29yZD48a2V5d29yZD5Qcm90ZWluIEtpbmFzZSBDL2FudGFnb25pc3RzICZhbXA7IGluaGliaXRvcnM8L2tleXdvcmQ+PGtleXdvcmQ+UmF0czwva2V5d29yZD48a2V5d29yZD5SYXRzLCBTcHJhZ3VlLURhd2xleTwva2V5d29yZD48a2V5d29yZD5TaWduYWwgVHJhbnNkdWN0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlRyYW5zZmVjdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA2PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+QXVnIDQ8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xNTI0LTQ1NzEgKEVsZWN0cm9uaWMpJiN4RDswMDA5LTczMzAgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE2ODA5NTUyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzE2ODA5NTUyPC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMTYxLzAxLlJFUy4wMDAwMjM0NzgwLjA2MTE1LjJjPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn== ADDIN EN.CITE.DATA 96, PICOT does so by inhibiting the activity of NF-AT signaling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 97, 98.2.2.2.4. NF- kB signaling;NF-kB (Nuclear factor kappa- light- chain- enhancer of activated B cell) is the protein complex that controls transcription. The pathway is involved in B-cell maturation and lymphoid organogenesis hence plays a great role in immune system and response. It is reported to be activated by cytokines, reactive oxygen species, bacterial cell wall products, viral infections, vasopressors and DNA damage ADDIN EN.CITE <EndNote><Cite><Author>Brasier</Author><Year>2006</Year><RecNum>56</RecNum><DisplayText>99</DisplayText><record><rec-number>56</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1515589293″>56</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Brasier, A. R.</author></authors></contributors><auth-address>Department of Internal Medicine and Sealy Center for Molecular Sciences, University of Texas Medical Branch, Galveston, TX 77555-1060, USA. [email protected]</auth-address><titles><title>The NF-kappaB regulatory network</title><secondary-title>Cardiovasc Toxicol</secondary-title><alt-title>Cardiovascular toxicology</alt-title></titles><periodical><full-title>Cardiovasc Toxicol</full-title><abbr-1>Cardiovascular toxicology</abbr-1></periodical><alt-periodical><full-title>Cardiovasc Toxicol</full-title><abbr-1>Cardiovascular toxicology</abbr-1></alt-periodical><pages>111-30</pages><volume>6</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Biotransformation/physiology</keyword><keyword>Cell Nucleus/physiology</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/physiology</keyword><keyword>NF-kappa B/genetics/*physiology</keyword><keyword>Signal Transduction/physiology</keyword></keywords><dates><year>2006</year></dates><isbn>1530-7905 (Print) 1530-7905 (Linking)</isbn><accession-num>17303919</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17303919</url></related-urls></urls></record></Cite></EndNote>99. Under normal conditions, the pathway is inactive where NIK (NF-kB inducing kinase) is bound to a protein complex of TRAF3 (TNF receptor associated factor 3), TRAF2 (TNF receptor associated factor 2) and CiAP1/2 (cellular inhibitor of apoptosis 1 and 2). The latter protein, ubiquinate NIK leading into proteasome degradation hence NIK is maintained in low levels. When the ligand binds the receptor, NIK is released from the complex and it phosphorylates IKK?. Activated IKK?, interacts with inactive protein dimer of P100/RelB which leads into a formation of a new protein dimer P52/RelB. The P52/RelB enter the nucleus and initiate the transcription of genes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 100, 101 and promote its functions like inflammation, oncogenesis, cell growth and differentiation 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ADDIN EN.CITE.DATA 102. It also plays a great role in cardiovascular growth and gene network expression in inflammation ADDIN EN.CITE <EndNote><Cite><Author>Brasier</Author><Year>2006</Year><RecNum>56</RecNum><DisplayText>99</DisplayText><record><rec-number>56</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1515589293″>56</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Brasier, A. R.</author></authors></contributors><auth-address>Department of Internal Medicine and Sealy Center for Molecular Sciences, University of Texas Medical Branch, Galveston, TX 77555-1060, USA. [email protected]</auth-address><titles><title>The NF-kappaB regulatory network</title><secondary-title>Cardiovasc Toxicol</secondary-title><alt-title>Cardiovascular toxicology</alt-title></titles><periodical><full-title>Cardiovasc Toxicol</full-title><abbr-1>Cardiovascular toxicology</abbr-1></periodical><alt-periodical><full-title>Cardiovasc Toxicol</full-title><abbr-1>Cardiovascular toxicology</abbr-1></alt-periodical><pages>111-30</pages><volume>6</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Biotransformation/physiology</keyword><keyword>Cell Nucleus/physiology</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/physiology</keyword><keyword>NF-kappa B/genetics/*physiology</keyword><keyword>Signal Transduction/physiology</keyword></keywords><dates><year>2006</year></dates><isbn>1530-7905 (Print) 1530-7905 (Linking)</isbn><accession-num>17303919</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17303919</url></related-urls></urls></record></Cite></EndNote>99. Figure SEQ Figure * ARABIC 7; NF-KB signaling pathway activation.Upon activation by Cardiac hypertrophic agonists, Gq-coupled receptors activate PKC, which can lead to activation of NF-?B through degradation of I?B?. Activated NF-?B-p50 and NF-?B-p65 proteins in cytoplasm move into nucleus where they bind to the promoter of GRK5. This activated protein complex may interact with other transcription factors and coactivators in the promoter region, thereby enhancing the transcription of GRK5. As ROS have shown to be important in the process of activation, NF-KB inhibitors like antioxidants can block the whole event of activation.Very few studies have been done in the involvement of NF-kB pathway in the pathogenesis of HCM. NF-kB regulates inflammatory genes and circulating inflammatory cytokines are raised in patients with HCM. Johanna et al found low-grade myocardial inflammation in endomyocardial samples and in the circulation of patients with HCM. These cytokines correlated with the histopathological myocardial fibrosis. In this study the NF-kB activity was high suggesting it to be a cause of myocardial fibrosis in HCM 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 103. In myocarditis and other inflammatory cardiomyopathies, NF-kB activation was found to be the most important pathway 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 104. There are existing evidences on NF-kB pathway activation in some cases of cardiac hypertrophy with causes other than HCM. The clear pathway on how it is involved is still yet to be discovered but the interleukin (IL) family of cytokines like IL-6, have been studied to cause cardiac myocyte hypertrophy through NF-kB activation ADDIN EN.CITE <EndNote><Cite><Author>Gordon</Author><Year>2011</Year><RecNum>96</RecNum><DisplayText>105</DisplayText><record><rec-number>96</rec-number><foreign-keys><key app=”EN” db-id=”derfet0zk9wxsretp09pzwxrx50dfvxar592″ timestamp=”1519901619″>96</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Gordon, J. W.</author><author>Shaw, J. A.</author><author>Kirshenbaum, L. A.</author></authors></contributors><auth-address>Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.</auth-address><titles><title>Multiple facets of NF-kappaB in the heart: to be or not to NF-kappaB</title><secondary-title>Circ Res</secondary-title><alt-title>Circulation research</alt-title></titles><periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></periodical><alt-periodical><full-title>Circ Res</full-title><abbr-1>Circulation research</abbr-1></alt-periodical><pages>1122-32</pages><volume>108</volume><number>9</number><keywords><keyword>Animals</keyword><keyword>Apoptosis/*physiology</keyword><keyword>Autophagy/physiology</keyword><keyword>Cytokines/physiology</keyword><keyword>*Heart Failure/metabolism/pathology/physiopathology</keyword><keyword>Humans</keyword><keyword>Myocytes, Cardiac/*pathology/physiology</keyword><keyword>NF-kappa B/*physiology</keyword><keyword>Necrosis</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 29</date></pub-dates></dates><isbn>1524-4571 (Electronic) 0009-7330 (Linking)</isbn><accession-num>21527742</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21527742</url></related-urls></urls><electronic-resource-num>10.1161/CIRCRESAHA.110.226928</electronic-resource-num></record></Cite></EndNote>105. In a transgenic mouse model of TGT400N with cardiac hypertrophy, NF-kB was among the pathways activated and Akt/mTor being the other 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ADDIN EN.CITE.DATA 106. NF-kB have been reported to be an important factor in the initiation and cardiac hypertrophy and progression of it to heart failure, this was supported by the increase in activity of this pathway during these two phases and its inhibition with PDTC appeared to improve the cardiac function in these animal 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ADDIN EN.CITE.DATA 107. NF-kB signaling as a cause of cardiac hypertrophy in HCM have not been studied which warrants further research.ROS have been involved in activating NF-kB in a number of activities. During cardiac hypertrophy, the normal pattern of cardiac gene expression is altered which provide different outcome. A number of transcription factors are involved in this alteration including NF-kB where ROS have been reported to activate them during the process ADDIN EN.CITE <EndNote><Cite><Author>Sag</Author><Year>2014</Year><RecNum>282</RecNum><DisplayText>108</DisplayText><record><rec-number>282</rec-number><foreign-keys><key app=”EN” db-id=”at0d2e224rdzf1e9fpbpt59f9txsprx9wt02″>282</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Sag, C. M.</author><author>Santos, C. X. C.</author><author>Shah, A. M.</author></authors></contributors><auth-address>British Heart Fdn Ctr Excellence, Kings Coll London, Div Cardiovasc, London, England</auth-address><titles><title>Redox regulation of cardiac hypertrophy</title><secondary-title>Journal of Molecular and Cellular Cardiology</secondary-title><alt-title>J Mol Cell Cardiol</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>103-111</pages><volume>73</volume><keywords><keyword>hypertrophy</keyword><keyword>cardiac</keyword><keyword>redox</keyword><keyword>signaling</keyword><keyword>nadph oxidase</keyword><keyword>nitric-oxide synthase</keyword><keyword>induced cardiomyocyte hypertrophy</keyword><keyword>nox2-containing nadph oxidase</keyword><keyword>disulfide bond formation</keyword><keyword>heart-failure</keyword><keyword>myocardial-infarction</keyword><keyword>angiotensin-ii</keyword><keyword>sarcoplasmic-reticulum</keyword><keyword>pressure-overload</keyword><keyword>oxidative stress</keyword></keywords><dates><year>2014</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0022-2828</isbn><accession-num>WOS:000337551000013</accession-num><urls><related-urls><url>&lt;Go to ISI&gt;://WOS:000337551000013</url></related-urls></urls><electronic-resource-num>10.1016/j.yjmcc.2014.02.002</electronic-resource-num><language>English</language></record></Cite></EndNote>108. Studies in mouse models showed NOX2 dependent activation of NF-kB and matrix metalloproteinase in causing cardiac interstitial fibrosis ADDIN EN.CITE <EndNote><Cite><Author>Sag</Author><Year>2014</Year><RecNum>282</RecNum><DisplayText>108</DisplayText><record><rec-number>282</rec-number><foreign-keys><key app=”EN” db-id=”at0d2e224rdzf1e9fpbpt59f9txsprx9wt02″>282</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Sag, C. M.</author><author>Santos, C. X. C.</author><author>Shah, A. M.</author></authors></contributors><auth-address>British Heart Fdn Ctr Excellence, Kings Coll London, Div Cardiovasc, London, England</auth-address><titles><title>Redox regulation of cardiac hypertrophy</title><secondary-title>Journal of Molecular and Cellular Cardiology</secondary-title><alt-title>J Mol Cell Cardiol</alt-title></titles><periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></periodical><alt-periodical><full-title>J Mol Cell Cardiol</full-title><abbr-1>Journal of molecular and cellular cardiology</abbr-1></alt-periodical><pages>103-111</pages><volume>73</volume><keywords><keyword>hypertrophy</keyword><keyword>cardiac</keyword><keyword>redox</keyword><keyword>signaling</keyword><keyword>nadph oxidase</keyword><keyword>nitric-oxide synthase</keyword><keyword>induced cardiomyocyte hypertrophy</keyword><keyword>nox2-containing nadph oxidase</keyword><keyword>disulfide bond formation</keyword><keyword>heart-failure</keyword><keyword>myocardial-infarction</keyword><keyword>angiotensin-ii</keyword><keyword>sarcoplasmic-reticulum</keyword><keyword>pressure-overload</keyword><keyword>oxidative stress</keyword></keywords><dates><year>2014</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0022-2828</isbn><accession-num>WOS:000337551000013</accession-num><urls><related-urls><url>&lt;Go to ISI&gt;://WOS:000337551000013</url></related-urls></urls><electronic-resource-num>10.1016/j.yjmcc.2014.02.002</electronic-resource-num><language>English</language></record></Cite></EndNote>108. Mice with genetically increased NOX4 had higher levels of oxidative stress and developed cardiac hypertrophy via activated Akt/mTor and NF-kB pathway, using antioxidant the activated pathways were reduced so did the cardiac hypertrophy ADDIN EN.CITE <EndNote><Cite><Author>Xu</Author><Year>2016</Year><RecNum>285</RecNum><DisplayText>109</DisplayText><record><rec-number>285</rec-number><foreign-keys><key app=”EN” db-id=”at0d2e224rdzf1e9fpbpt59f9txsprx9wt02″>285</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Xu, L. F.</author><author>Brink, M.</author></authors></contributors><auth-address>Univ Basel, Dept Biomed, Hebelstr 20, CH-4031 Basel, Switzerland Univ Basel Hosp, Hebelstr 20, CH-4031 Basel, Switzerland</auth-address><titles><title>mTOR, cardiomyocytes and inflammation in cardiac hypertrophy</title><secondary-title>Biochimica Et Biophysica Acta-Molecular Cell Research</secondary-title><alt-title>Bba-Mol Cell Res</alt-title></titles><periodical><full-title>Biochimica Et Biophysica Acta-Molecular Cell Research</full-title><abbr-1>Bba-Mol Cell Res</abbr-1></periodical><alt-periodical><full-title>Biochimica Et Biophysica Acta-Molecular Cell Research</full-title><abbr-1>Bba-Mol Cell Res</abbr-1></alt-periodical><pages>1894-1903</pages><volume>1863</volume><number>7</number><keywords><keyword>protein synthesis</keyword><keyword>protein degradation</keyword><keyword>mtor</keyword><keyword>nf-kappab</keyword><keyword>inflammation</keyword><keyword>cardiomyocyte</keyword><keyword>nf-kappa-b</keyword><keyword>ubiquitin-proteasome system</keyword><keyword>protein-kinase-c</keyword><keyword>focal adhesion kinase</keyword><keyword>p70 s6 kinase</keyword><keyword>mammalian target</keyword><keyword>heart-failure</keyword><keyword>molecular-mechanisms</keyword><keyword>pressure-overload</keyword><keyword>signaling pathways</keyword></keywords><dates><year>2016</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0167-4889</isbn><accession-num>WOS:000378360400023</accession-num><urls><related-urls><url>&lt;Go to ISI&gt;://WOS:000378360400023</url></related-urls></urls><electronic-resource-num>10.1016/j.bbamcr.2016.01.003</electronic-resource-num><language>English</language></record></Cite></EndNote>109The role of ROS activating NF-kB pathway plays in the development cardiac hypertrophy was proved further by the studies on mice where treatment with pyrrolidine dithiocarbamate (PDTC) an antioxidant that inhibit NF-kB through direct oxidation of thiols on 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ADDIN EN.CITE.DATA 110, prevented the development of cardiac 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ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>2004</Year><RecNum>75</RecNum><DisplayText>[81, 110, 111]</DisplayText><record><rec-number>75</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515757779">75</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, Y.</author><author>Ha, T.</author><author>Gao, X.</author><author>Kelley, J.</author><author>Williams, D. L.</author><author>Browder, I. W.</author><author>Kao, R. L.</author><author>Li, C.</author></authors></contributors><auth-address>Dept. of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Campus Box 70575, Johnson City, TN 37614-0575, USA. Li@mail.etsu.edu</auth-address><titles><title>NF-kappaB activation is required for the development of cardiac hypertrophy in vivo</title><secondary-title>Am J Physiol Heart Circ Physiol</secondary-title><alt-title>American journal of physiology. Heart and circulatory physiology</alt-title></titles><periodical><full-title>Am J Physiol Heart Circ Physiol</full-title><abbr-1>American journal of physiology. Heart and circulatory physiology</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Heart Circ Physiol</full-title><abbr-1>American journal of physiology. Heart and circulatory physiology</abbr-1></alt-periodical><pages>H1712-20</pages><volume>287</volume><number>4</number><keywords><keyword>Adenoviridae/genetics</keyword><keyword>Animals</keyword><keyword>Antioxidants/pharmacology</keyword><keyword>Aorta/physiopathology</keyword><keyword>Atrial Natriuretic Factor/genetics</keyword><keyword>Cardiomegaly/*metabolism/pathology</keyword><keyword>I-kappa B Kinase</keyword><keyword>I-kappa B Proteins/genetics</keyword><keyword>Ligation</keyword><keyword>Male</keyword><keyword>Myocardium/*metabolism/pathology</keyword><keyword>NF-KappaB Inhibitor alpha</keyword><keyword>NF-kappa B/*metabolism</keyword><keyword>Natriuretic Peptide, Brain/genetics</keyword><keyword>Proline/*analogs &amp; derivatives/pharmacology</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Thiocarbamates/pharmacology</keyword><keyword>Transfection</keyword></keywords><dates><year>2004</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0363-6135 (Print)&#xD;0363-6135 (Linking)</isbn><accession-num>15142841</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15142841</url></related-urls></urls><electronic-resource-num>10.1152/ajpheart.00124.2004</electronic-resource-num></record></Cite><Cite><Author>Xu</Author><Year>2016</Year><RecNum>76</RecNum><record><rec-number>76</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515758402">76</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Xu, L.</author><author>Brink, M.</author></authors></contributors><auth-address>Department of Biomedicine, University of Basel and University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.&#xD;Department of Biomedicine, University of Basel and University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. Electronic address: marijke.brink@unibas.ch.</auth-address><titles><title>mTOR, cardiomyocytes and inflammation in cardiac hypertrophy</title><secondary-title>Biochim Biophys Acta</secondary-title><alt-title>Biochimica et biophysica acta</alt-title></titles><periodical><full-title>Biochim Biophys Acta</full-title><abbr-1>Biochimica et biophysica acta</abbr-1></periodical><alt-periodical><full-title>Biochim Biophys Acta</full-title><abbr-1>Biochimica et biophysica acta</abbr-1></alt-periodical><pages>1894-903</pages><volume>1863</volume><number>7 Pt B</number><keywords><keyword>Animals</keyword><keyword>Cardiomegaly/drug therapy/*enzymology/genetics/pathology/physiopathology</keyword><keyword>Cardiovascular Agents/pharmacology</keyword><keyword>Humans</keyword><keyword>Inflammation Mediators/*metabolism</keyword><keyword>Myocarditis/drug therapy/*enzymology/genetics/pathology/physiopathology</keyword><keyword>Myocytes, Cardiac/drug effects/*enzymology/pathology</keyword><keyword>Protein Biosynthesis</keyword><keyword>Protein Kinase Inhibitors/pharmacology</keyword><keyword>Proteolysis</keyword><keyword>Signal Transduction</keyword><keyword>TOR Serine-Threonine Kinases/antagonists &amp; inhibitors/genetics/*metabolism</keyword><keyword>Ventricular Remodeling</keyword></keywords><dates><year>2016</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0006-3002 (Print)&#xD;0006-3002 (Linking)</isbn><accession-num>26775585</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/26775585</url></related-urls></urls><electronic-resource-num>10.1016/j.bbamcr.2016.01.003</electronic-resource-num></record></Cite><Cite><Author>Mariappan</Author><Year>2010</Year><RecNum>77</RecNum><record><rec-number>77</rec-number><foreign-keys><key app="EN" db-id="derfet0zk9wxsretp09pzwxrx50dfvxar592" timestamp="1515758975">77</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mariappan, N.</author><author>Elks, C. M.</author><author>Sriramula, S.</author><author>Guggilam, A.</author><author>Liu, Z.</author><author>Borkhsenious, O.</author><author>Francis, J.</author></authors></contributors><auth-address>Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.</auth-address><titles><title>NF-kappaB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes</title><secondary-title>Cardiovasc Res</secondary-title><alt-title>Cardiovascular research</alt-title></titles><periodical><full-title>Cardiovasc Res</full-title><abbr-1>Cardiovascular research</abbr-1></periodical><alt-periodical><full-title>Cardiovasc Res</full-title><abbr-1>Cardiovascular research</abbr-1></alt-periodical><pages>473-83</pages><volume>85</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Body Weight</keyword><keyword>Diabetes Mellitus, Type 2/*physiopathology</keyword><keyword>Echocardiography</keyword><keyword>Electron Transport Complex III/metabolism</keyword><keyword>Glutathione/analysis</keyword><keyword>Heart/*physiopathology</keyword><keyword>Interleukin-6/blood</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mitochondria/*physiology</keyword><keyword>NF-kappa B/analysis/antagonists &amp; inhibitors/*physiology</keyword><keyword>Organ Size</keyword><keyword>*Oxidative Stress</keyword><keyword>Reactive Oxygen Species/metabolism</keyword><keyword>Superoxides/metabolism</keyword><keyword>Tumor Necrosis Factor-alpha/blood</keyword></keywords><dates><year>2010</year><pub-dates><date>Feb 1</date></pub-dates></dates><isbn>1755-3245 (Electronic)&#xD;0008-6363 (Linking)</isbn><accession-num>19729361</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19729361</url></related-urls></urls><custom2>2860708</custom2><electronic-resource-num>10.1093/cvr/cvp305</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 81, 110, 111CHAPTER 3: METHODOLOGY.3.1. STUDY DESIGN3.1.1. Type and site of the studyThe study was a prospective experimental design conducted at Wuhan Union hospital, Wuhan city, Hubei province in Peoples’ Republic of China.3.1.2. Study populationThe study sample was taken from the heart sample after heart transplant from the patients who were diagnosed to have congenital Hypertrophic cardiomyopathy.Inclusion criteria.Samples from children below 14 years, which is the age group considered as pediatric patient.Samples that had already been proven by the pathologist to have pathological features of hypertrophic cardiomyopathy.Exclusion criteria.Age above 14 years, adult patients.Cardiac hypertrophy due to other causes other that genetic hypertrophic cardiomyopathy such as hypertension. Samples with no pathological features of genetic hypertrophic cardiomyopathy.3.2. PATIENT’S HISTORY;From the above inclusion and Exclusion criteria and the timeline of our study we were able to obtain three heart samples that had Hypertrophic cardiomyopathy and one control sample. In the diseased heart sample, the first heart and the second heart were from patients with diastolic dysfunction, while the third heart was from a patient having systolic dysfunction heart failure judged from the ejection fraction and the appearance of the heart. 3.2.1. Patient 1;Patient ZYAge; 8 years and 3 months oldSex; FemalePatient treated with recurrent episode of pneumonia from local hospital. She currently presented to the hospital with difficulty in breathing, chest tightness and lower limb edema. Upon investigation, she was diagnosed to have restrictive cardiomyopathy and was referred to our hospital for further management. o/e conscious, well oriented to time, place and person, lethargic, nasal flaring and lower limb edema. Pulse rate 80 beats/min, Respiratory rate 30 cycles/min, BP 90/60 mmHg and Temperature of 36.8C.Respiratory systemSupraclavicular, intercostals and sub costal retractionsBronchial breath sounds and wet rales in the lower left lung fieldBasal crepitationsCardiovascular systemBlood pressure of 93/61 mmHgApex beat on the 6th intercostals space 1cm lateral to the mid clavicular lineEchocardiography;Thickening of the ventricular walls more on the left ventricle Features of interstitial fibrosisEjection fraction of 54%Diagnosis; Heart failure secondary to restrictive cardiomyopathy and severe pneumonia.Management;Antibiotics due pneumoniaMedications for heart failureHeart transplant done after two weeksPathology of the heart tissue reveled, interstitial fibrosis, myocyte hypertrophy and myocyte disarray which confirmed the diagnosis of Hypertrophic cardiomyopathy.3.2.2. Patient 2; Patient JC, Age: 11 years and 2 months oldSex: Male childHe was a known case of Restrictive cardiomyopathy, which was diagnosed from Shanghai Children’s Hospital since 2 years ago. Chief complains: Fever, cough and Difficulty in breathing. The cough was productive with expectoration of yellow sputum and had severe chest pain.Past history: Two years ago, he presented to the local hospital with repeated episodes of fever and productive cough and after investigations they noted a heart disease, was then referred to Shanghai Children’s hospital where was diagnosed to have Restrictive cardiomyopathy. The child was given antibiotics and symptomatic cardiac medications like captopril, Furosemide, Spironolactone and Aspirin. The symptoms were controlled for sometime but after one year, he presented with severe respiratory distress, severe body weakness, lower limb edema and shortness of breath after minor activity. He was then diagnosed to have severe pneumonia and heart failure. Intravenous antibiotics were administered together with cardiotonic drugs were added to the cardiac medications. Symptoms improved but from this time he started having recurrent admissions due to severe pneumonia and heart failure, which ended up with the referral for possible heart transplant. No history of Hepatitis or Tuberculosis was reported. No history of surgery or blood transfusion before. Review of other systems: Other systems like the gastrointestinal system, central nervous system, genital urinary system, Musculoskeletal and endocrine systems were essentially normal.Family history: No history of similar illness was reported in the family. Physical examination: conscious, alert, oriented to time place and person, normal skin color, no rashes and had lower limb edema. Vitals; temperature 36.5C, pulse rate 90 Beats/min, BP 79/59 mmHg, respiratory rate 20 Cycles/min. He had a weight of 24kg and the height of 137 cm. In here we noticed the patient having poor growth and hypotensive. Systemic examination: Respiratory system; coarse breath sounds and basal crepitationCardiovascular system; Heart rate of 88 Beats/min, no obvious murmur was reported.Gastrointestinal system; Hepatomegaly, 3 Cm below the right costal marginCentral nervous system, Genital-urinary system, musculoskeletal systems were essentially normalEchocardiography from Shanghai children’s hospital; Bilateral atrial enlargement, left ventricular hypertrophy, mild to moderate mitral regurgitation, left ventricular systolic function was in the lower limit of normal, diastolic dysfunction.The echocardiography in our hospital showed the right and left atrium to be increased significantly and there was left ventricular inhomogeneous thickening. The left heart function decreased; the left ventricular basal segment and interventricular septal myocardial interstitial band low signal perfusion defect, delayed enhancement scan suspected myocardial fibrosis; mild mitral insufficiency; interstitial pulmonary edema and hepatic congestion;the ejection fraction was 51%.Gene sequencing from Shanghai Children’s hospital; missense mutation in the TNN13 geneDiagnoses:Heart failure NYHA stage IV secondary to Hypertrophic cardiomyopathyDdx- Restrictive cardiomyopathySevere pneumonia Management;AntibioticsCardiac medications like Metoprolol, Furosemide, captopril, sodium nitroprusideAfter 1week Heart transplant was done due to rapid deterioration of the condition.Pathological report; Myocyte hypertrophy, interstitial fibrosis and myocyte disarray.3.2.3. Patient 3;Patient RHAge; 11 years and six monthsSex; female History of the present illiness;One year before the admission patient presented in the local hospital with sudden onset of shortness of breath, chest tightness, nausea, and vomiting and abdominal discomfort. Upon different examination, color Doppler ultrasonography showed severe mitral valve regurgitation where mitral valvuloplasty was opted and was done successfully. The patient was then discharged with medication like digoxin, Betaloc, Furosemide, Spironolactone, captopril to improve and enhance cardiac function. Two months later, symptoms of chest tightness and shortness of breathe reappeared and currently she developed Oliguria and edema of the lower extremities. Echocardiography showed severe mitral and tricuspid valves regurgitation, severe double ventricular functional impairment with Left ventricular ejection fraction of 20% and the right ventricular ejection fraction of 30%. Had also mild aortic regurgitation, pulmonary hypertension and mild pulmonary valve regurgitation. She was then referred to our hospital with the possible diagnosis of heart failure secondary to dilated cardiomyopathy for possible heart transplantation.During Admission;On Examination; the patient was conscious, well oriented to time, place and person, had dyspnea with supraclavicular, intercostal and subcostal retractions and had lower limb edema. The vitals; temperature of 36.3C, pulse rate 120 Beats/min, Respiratory rate 20 cycles/min, BP 87/59 mmHg, weight of 34 kg. Echocardiography; Left ventricular basal segment, middle segment, inferior wall and lateral wall endocardial non-compact myocardium with delayed enhancement and suggestive of myocardial fibrosis.Myocardial thickeningEnlarged left ventricle and left cardiac function significantly reduced with ejection fraction (EF) of 17%Mitral valve changes associated with severe mitral insufficiency.Widened pulmonary artery and inferior vena cava. Chest X-ray; Increased pulmonary blood flow suggesting pulmonary hypertension. Diagnoses; Heart failure NYHA stage IV secondary to dialated cardiomyopathySevere mitral regurgitation after mitral valvuloplasty. Management; heart transplant was done Pathology; cardiomyocyte hypertrophy, interstitial fibrosis. Features suggestive of hypertrophic cardiomyopathy.3.3. RESEARCH CONCEPTThe aim of the experiment was to prove and support the existence of increased oxidative stress in the hearts with hypertrophic cardiomyopathy (HCM) since oxidative stress was long being implicated as the important progressive factor for the expression of the disease.Reactive oxygen species (ROS) are very reactive molecules which makes it difficult to measure them directly, measuring their end product have long being used as a possible mechanism to measure them, one of the methods is through fluorescence microscopy of Dihydroethidium (DHE), which was the method employed in our experiment. DHE is a reduced form of DNA dyes Ethidium bromide; it has high reactivity and can diffuse passively into cells, hence used to detect cytosolic superoxide 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 112, 113. Upon reaction with superoxide anions, DHE forms a red fluorescent product 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ADDIN EN.CITE.DATA 114, which intercalates with DNA and exhibit red fluorescent ADDIN EN.CITE <EndNote><Cite><Author>Bucana</Author><Year>1986</Year><RecNum>23</RecNum><DisplayText>115</DisplayText><record><rec-number>23</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1517726921″>23</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Bucana, C.</author><author>Saiki, I.</author><author>Nayar, R.</author></authors></contributors><titles><title>Uptake and accumulation of the vital dye hydroethidine in neoplastic cells</title><secondary-title>J Histochem Cytochem</secondary-title><alt-title>The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society</alt-title></titles><periodical><full-title>J Histochem Cytochem</full-title><abbr-1>The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society</abbr-1></periodical><alt-periodical><full-title>J Histochem Cytochem</full-title><abbr-1>The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society</abbr-1></alt-periodical><pages>1109-15</pages><volume>34</volume><number>9</number><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Cytophotometry</keyword><keyword>Ethidium/*analogs &amp; derivatives/metabolism</keyword><keyword>Fibrosarcoma/*metabolism</keyword><keyword>Flow Cytometry</keyword><keyword>*Fluorescent Dyes</keyword><keyword>Humans</keyword><keyword>Melanoma/*metabolism</keyword><keyword>Mice</keyword><keyword>Microscopy, Fluorescence</keyword><keyword>Spectrometry, Fluorescence</keyword><keyword>*Staining and Labeling</keyword></keywords><dates><year>1986</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0022-1554 (Print) 0022-1554 (Linking)</isbn><accession-num>2426339</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/2426339</url></related-urls></urls><electronic-resource-num>10.1177/34.9.2426339</electronic-resource-num></record></Cite></EndNote>115. DHE cannot only be used to detect superoxide but also ONOO and OH 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 112, 116. 3.4. MATERIALSMaterials used in this study were; Na2HPO4.12H2ONaH2PO4.2H2ODistilled waterSucroseDihydroethidium powder (DHE)HBSS solution (Hank’s Balanced Salt Solution)DMSO solution (Anhydrous dimethyl sulfoxide)PipetteFilter paperOCT compound (Optimal Cutting Temperature Compound)Dark boxCentrifugeStop watchMicrotome Glass slidesRefrigeratorSterile glass boxFluorescent microscopy3.5. METHODS3.5.1. Making PB solution0.2 Mol/L of PB solution was made by mixing 14.505g of Na2HPO4.12H2O, 1.4815g of NaH2PO4.2H2O and 250mls of distilled water.3.5.2. Making 30% sucrose solution15.0g of sucrose were mixed with 25.0 mls of PB solution and 25.0 mls of distilled water.3.5.3. Making 20% sucrose solution10g of sucrose was mixed with 25.0mls of PB solution and 25.0 mls of distilled water.3.5.4. Making the store solutionDHE is in powder form, to make a solution, 5mg of DHE was dissolved in 3.17 mls of DMSO solution, and the mixture was then centrifuged to mix properly. The solution produced was 5mMol of DHE that is a store solution stored in -20C refrigerator.3.5.5. Making a working solutionFrom the store solution, a working solution of 50nMol DHE was made by mixing 5mMol of DHE with HBSS solution in a ratio of 1 to 98. The solution is then centrifuged to ensue complete mixing.3.5.6. Fixing and slicing the heart samplesDifferent chambers of the heart pieces were first put in 20% sucrose solution for 12 hours and then in 30% sucrose solution for another 12 hours. This process made the heart tough and tenacious for slicingFrom 30% sucrose solution, the heart pieces were put in the OCT compound ready to be sliced.The heart pieces were then sliced with a microtome into 5?m thin pieces and put into the glass slides ready for staining. 3.5.7. Staining of the heart samples and ROS visualization.Three drops of the DHE working solution were dropped on every heart sample on the slide and were left for 60 minutes to allow staining. Because DHE is affected by light, this process was done in the dark box to prevent light interference. After 60 minutes, the slides were washed with HBSS solution for 5 minutes three times. And this was also done in the dark box.ROS was then visualized under fluorescent microscope under the blue light.3.5.8. AnalysisThe fluorescent images were analyzed using the IMAGE J program so as to get the numerical data for statistical analysis. Then SPSS version 24 was used for statistical analysis. First ANOVA test as used to compare the mean differences in oxidative stress between the four heart chambers in each heart and the normal and then Post- hoc test for Anova was used to compare specific group differences. The tests compared 3.6. ETHICAL CONSIDERATIONThis study was made possible after being approved by my academic supervisor, the head of pediatric department of Wuhan Union Hospital of China, Tongji Medical College of Huazhong University of Science and Technology (HUBEI, CHINA).The research was conducted in considering good clinical practice guidelines and we respected all the applicable regulatory rules under the guiding principles of the Declaration of Helsinki.CHAPTER 4: RESULTS4.1. Microscopy images and Image J analysisAfter fluorescent microscopy of the fixed sections, images were taken. The red dots in the images represented the oxidative stress present in the sections. Below are some of the images that were obtained from different sections of different chambers of the hearts.left179705a bc de fg hFigure SEQ Figure * ARABIC 8; fluorescent microscopy images showing ROS in different heart chambers with HCM. The red bright dots in the slides are the ROS that were stained after DHE staining and visualized in green fluorescent light. a. Left ventricle of the third patient’s heart; b. Inter-ventricular septum of the third patient’s heart; c. Right ventricle in the third patient’s heart; d. Right atrium in the third patient’s heart; e. Left ventricle of the seconds patient’s heart; f. Right atrium of the second patient’s heart; g. Right Atrium of normal heart; h. Right Atrium normal heart. ROS were mostly noticed in the Left ventricle slides than others.The images were then analyzed using Image J program to obtain pixel values of ROS in the fluorescent images. a bc de fg hFigure 9; Image j analysis of the above fluorescent images from figure 8. The black dotes denotes ROS for easy visualization4.2. SPSS statistical analysis.Four hearts were analyzed differently and the comparison was made between the oxidative stress of the diseased heart and the normal heart.4.2.1. Analysis of the First heart.Table SEQ Table * ARABIC 1: Description statistics of the first heart. Heart Chambers N Mean Std. Deviation 95% Confidence Interval for Mean Minimum MaximumLower Bound Upper Bound Intden-LV 100 17766.42 10238.074 15734.96 19797.88 7430 99420Intden-RV 100 7496.84 3266.349 6848.73 8144.95 1969 16777Intden-IV 100 9768.28 2962.194 9180.52 10356.04 1908 17993Intden-RA 100 5331.65 3003.573 4735.68 5927.62 1156 23435Intden-Normal 100 2126.51 1091.42 1909.95 2343.07 147 4976Total 500 8497.94 7386.698 7848.91 9146.97 147 99420Figure SEQ Figure * ARABIC 10; bar chart showing the mean amount of reactive oxygen species in the heart chambers of the first patient’s heart. The left ventricle had the highest amount of reactive oxygen species followed by the interventricular septim, the right ventricle, the right atrium and lastly the normal heart.In the first heart, the left ventricle had the highest oxidative stress with highest amount of reactive oxygen species measured. The mean reactive oxygen species were 17766.42 units with the standard deviation of 10238.074 units. The 95% confidence interval was 15734.96 – 19797.88. The Inter-ventricular septum followed with the mean reactive oxygen species of 9768.28 units with a standard deviation of 2962.194 and a 95% confidence interval of 9180.52 – 10356.04. The Right ventricle followed the list with mean of 7496.84 unit of reactive oxygen species with the standard deviation of 3266.349 and a 95% confidence interval of 6848.73 – 8144.95. The Right atrium had the least amount of reactive oxygen species compared to the rest of the heart chambers with the mean of 5331.65 and a standard deviation of 3003.573 with a 95% confidence interval of 4735.68 – 5927.62. The normal heart chamber had the mean reactive oxygen species of 2126.51 units and a standard deviation of 1091.42 from the mean with a 95% confidence interval of 1909.95 – 2343.07. Seeing the difference in oxidative stress between the heart chambers, the significance of the difference were found using ANOVA test since we compared more than three means. Table SEQ Table * ARABIC 2: ANOVA of ROS in the first heartSum of Squares dfMean Square F Sig.Between Groups 13914119905 4 3478529976 129.338 <0.0001Within Groups 13312970782 495 26894890.47 Total 27227090686 499 From the ANOVA tests we found a significant difference in the oxidative stress between heart chambers which was described as F= 129.338, df= 4 and a p value of <0.0001. Since there was significance, we went further to conduct a post – Hoc ANOVA test to find which chambers had a significant difference among them. The Turkeys Post- Hoc test was used, as there was equal N value in all the chambers. Table SEQ Table * ARABIC 3: Multiple comparison of ROS in the first heartDependent Variable: level of oxidative stress Tukey HSD Section groups Section groups Mean Difference Sig. 95% Confidence IntervalLower Bound Upper BoundIntden-LV Intden-RV 10269.580* <0.0001 8261.59 12277.57Intden-IV 7998.140* <0.0001 5990.15 10006.13Intden-RA 12434.770* <0.0001 10426.78 14442.76Intden-Normal 15639.910* <0.0001 13631.92 17647.9Intden-RV Intden-IV -2271.440* 0.018 -4279.43 -263.45Intden-RA 2165.190* 0.027 157.2 4173.18Intden-Normal 5370.330* <0.0001 3362.34 7378.32Intden-IV Intden-RA 4436.630* <0.0001 2428.64 6444.62Intden-Normal 7641.770* <0.0001 5633.78 9649.76Intden-RA Intden-Normal 3205.140* <0.0001 1197.15 5213.13* The mean difference is significant at the 0.05 levels. From the post Hoc test, all the chambers had significant difference in mean reactive oxygen species from one another where between the Left Ventricle and Inter-ventricular septum, the left Ventricle and Right Ventricle, the Left Ventricle and Right Atrium, the Left Ventricle and Normal heart, the Right ventricle and the normal heart, the Inter-Ventricular septum and the right Atrium, The Inter-ventricular area and the Normal heart and the Right Atrium and the Normal heart, all had a significance in mean difference with a p value of <0.0001. For the Right Ventricle and the Inter-Ventricular site, there was a significant mean difference with the p value of 0.018 and the Right Ventricle and Right Atrium had a significant mean difference with the p value of 0.027. 4.2.2. Analysis of the second heart.Table SEQ Table * ARABIC 4: Descriptive statistic of ROS in the second heart Heart Chambers N Mean Std. Deviation 95% Confidence Interval for Mean MaximumLower Bound Upper Bound Minimum Intden-LV 65 14387.25 4692.534 13224.49 15550 6028 30326Intden-IV 65 16888.02 5880.873 15430.81 18345.22 6807 33924Intden-RV 65 6111.18 3797.71 5170.16 7052.21 513 16054Intden-RA 65 4568.09 2782.912 3878.52 5257.66 568 12254Intden-Normal 100 2126.51 1091.42 1909.95 2343.07 147 4976Total 360 8165.82 6958.546 7444.58 8887.07 147 33924Figure SEQ Figure * ARABIC 11; bar chart showing the mean value of ROS in different chambers of the second heart. The mean ROS in the inter-ventricular septum was the highest followed by the left ventricle then the right ventricle, the right Atrium and lastly the normal heart.In the second heart sample, the inter-ventricular area had high amount of reactive oxygen species than any other parts of the heart. The mean amount of reactive oxygen species was 16888.02 units with the standard deviation of 5880.873. The 95% confidence interval was 15430.81 – 18345.22. The left ventricle with mean reactive oxygen species of 14387.25 units followed the range with the standard deviation of 4692.534 and a 95% confidence interval of 13224.49 – 15550. Next in the list was the Right ventricle with mean reactive oxygen species of 6111.18 units with the standard deviation of 3797.71. Its 95% confidence interval is 5170.16 – 7052.21. The least amount of reactive oxygen species were found in the Right Atrium which had a mean of 4568.09 units of reactive oxygen species and a standard deviation of 2782.912. Its 95% confidence interval was 3878.52 – 5257.66 units. The same normal heart was compared as the first heart. Following the different values of Reactive oxygen species in the different heart chambers and the normal heart in general, the significance of the mean were found using Analysis Of Variance (ANOVA). This was used as we compared more than three means. Table SEQ Table * ARABIC 5: ANOVA of ROS in the second heartSum of Squares dfMean Square F Sig.Between Groups 12223946971 4 3055986743 210.275 <0.0001Within Groups 5159319909 355 14533295.52 Total 17383266881 359 From the ANOVA test, there was a significant difference in the means of reactive oxygen species between the heart chambers which was described by F= 210.275, df = 4 and a p value of <0.0001. To know which chambers had a significant difference in the level of reactive oxygen species, a Post Hoc ANOVA test was done and Scheffe post Hoc ANOVA test was used since the N value was different between sample groups. Table SEQ Table * ARABIC 6: Multiple comparison in the mean ROS in the second heartDependent Variable: level of oxidative stress Scheffe Section groups Section groups Mean Difference Sig. 95% Confidence IntervalLower Bound Upper BoundIntden-LV Intden-IV -2500.769* 0.008 -4571.45 -430.09Intden-RV 8276.062* <0.0001 6205.38 10346.74Intden-RA 9819.154* <0.0001 7748.47 11889.83Intden-Normal 12260.736* <0.0001 10379.95 14141.52Intden-IV Intden-RV 10776.831* <0.0001 8706.15 12847.51Intden-RA 12319.923* <0.0001 10249.24 14390.6Intden-Normal 14761.505* <0.0001 12880.72 16642.29Intden-RV Intden-RA 1543.092 0.258 -527.59 3613.77Intden-Normal 3984.675* <0.0001 2103.89 5865.46Intden-RA Intden-Normal 2441.582* 0.003 560.79 4322.37* The mean difference is significant at the 0.05 level. From the Post Hoc ANOVA test above, there was NO significant difference in the mean reactive oxygen species between the Right ventricle and Right Atrium. The was a significance difference in the mean reactive oxygen species between the Left Ventricle and Right Ventricle, Left ventricle and right Atrium, Left ventricle and Normal heart, Inter-ventricular septum and Right ventricle, Inter-Ventricular septum and Right Atrium, Inter-Ventricular Septum and Normal heart and Right Ventricle and the Normal ventricle with the p value <0.0001. how ever there was also significant difference in the mean Reactive oxygen species between the Left Ventricle and Inter-Ventricular septum with the P value of 0.008 and between Right Atrium and Normal heart with a P value of 0.003. 4.2.3. Analysis of the Third heart Sample.Table SEQ Table * ARABIC 7: Descriptive statistic of ROS in the third heartHeart chambers N Mean Std. Deviation 95% Confidence Interval for Mean Minimum MaximumLower Bound Upper Bound Intden-IV 100 9324.56 2639.536 8800.82 9848.31 4144 15508Intden-RV 100 8930.59 4720.279 7993.98 9867.2 1728 30508Intden-RA 100 3537.48 1782.385 3183.82 3891.14 861 10705Intden-LV 100 14972.38 5070.743 13966.23 15978.53 8059 36159Intden-Normal 100 2126.51 1091.42 1909.95 2343.07 147 4976Total 500 7778.3 5735.244 7274.38 8282.23 147 36159Figure SEQ Figure * ARABIC 12; bar chart showing mean value of ROS in different chambers of the third heart. The left ventricle had the highest mean ROS followed by the inter-ventricular region then the right ventricle, the right atrium and lastly the normal heart chamber.In the third heart, the left ventricle had high amount of Reactive Oxygen Species than any other heart chamber. Its mean amount of Oxidative stress was 14972.38 units with the standard deviation of 5070.743 from the mean. The 95% confidence interval was 13966.23 – 15978.53. This was followed by Inter-ventricular area with mean amount of oxidative stress 9324.56 units and a standard deviation of 2639.536 from the mean. The 95% confidence interval was 8800.82 – 9848.31. The Right Ventricle followed by close range to the Inter–Ventricular area, its mean amount of Reactive oxygen species was 8930.59 with a standard deviation of 4720.279 from the mean and a 95% confidence interval of 7993.98 – 9867.2. The lowest amount of reactive oxygen species was found in the Right Atrium, which had the mean of 3537.48 and the standard deviation of 1782.385 and the 95% confidence interval of 3183.82 – 3891.14. Again in this heart, the normal heart chamber seemed to have the lowest amount of reactive oxygen species compared to any chamber in the diseased heart. To find if the difference in the amount of Reactive Oxygen species was significant, the Analysis of Variance (ANOVA) test was conducted. Again this was used due to the fact that, more than three means were compared. The results are shown in the table belowTable SEQ Table * ARABIC 8; ANOVA of ROS in the third heart Sum of Squares dfMean Square F Sig.Between Groups 10540077541 4 2.64E+09 222.069 <0.0001Within Groups 5873542769 495 11865742.97 Total 16413620310 499 The ANOVA Test showed a significant difference in the mean reactive oxygen species between the heart chambers describes by the F= 222.069, df= 4 and p value <0.0001. To find which chambers exactly have significant difference in the mean oxidative stress, the Post –Hoc ANOVA test was conducted to precise the Turkey post Hoc ANOVA test because the sample size (N value) was the same in all the heart chambers. The results are well described below.Table SEQ Table * ARABIC 9: Multiple comparison of mean ROS from the third heartDependent Variable: Level of oxidative stress Turkey HSD Section groups Section groups Mean Difference Sig. 95% confidence intervalLower Bound Upper BoundIntden-IV Intden-RV 393.974 0.928 -939.77 1727.72Intden-RA 5787.084* <0.0001 4453.34 7120.83Intden-LV -5647.816* <0.0001 -6981.56 -4314.07Intden-Normal 7198.054* <0.0001 5864.31 8531.8Intden-RV Intden-RA 5393.110* <0.0001 4059.36 6726.86Intden-LV -6041.790* <0.0001 -7375.54 -4708.04Intden-Normal 6804.080* <0.0001 5470.33 8137.83Intden-RA Intden-LV -11434.900* <0.0001 -12768.65 -10101.15Intden-Normal 1410.970* 0.032 77.22 2744.72Intden-LV Intden-Normal 12845.870* <0.0001 11512.12 14179.62* The mean difference is significant at the 0.05 level The Post Hoc ANOVA test shows there is no significant difference in the mean reactive Oxygen species between the Inter-Ventricular area and the Right ventricle with the P value of 0.928. The significant difference in the mean Reactive Oxygen species existed between the Inter-Ventricular septum and the Right Atrium, inter-ventricular septum and the Left Ventricle, Inter-Ventricular septum and the normal heart chamber, Right ventricle and the Right Atrium, Right Ventricle and Left Ventricle, Right Ventricle and the normal heart chamber, Right Atrium and the Left Ventricle and the Normal heart chamber. In all these the p value was <0.0001. Moreover, there was also a significant difference in the mean Reactive Oxygen species between the right Atrium and the Normal heart chamber with the p value of 0.032. Though ROS was increased in all the three hearts, no heart had totally completely high ROS in all the chambers compared to the others. This means no single heart had completely increased oxidative stress compared to the other two hearts. Figure SEQ Figure * ARABIC 13; chamber wise comparison of mean ROS in the three hearts. The graphs show no one heart had the highest amount of ROS in all the chambers. While one heart had the highest mean ROS in one chamber, the other had the highest in another chamber.CHAPTER 5: DISCUSSIONHCM is the disease of sarcomere proteins and it affects heart muscles. Several evidences exist on the involvement of oxidative stress in the pathogenesis of the illness. Oxidative stress does affect cardiac myocytes in various ways like apoptosis, necrosis and even causing cardiac hypertrophy, which makes antioxidants as a potential therapeutic target for reversing cardiac hypertrophy phenotype in patients with HCM. Our research has proved the significant increase in oxidative stress in the patients with HCM as compared to the normal. This has been supported by a number of experiments done. To start with, many experiments measured the serum levels of indicators of oxidative stress like 8-Isoprostaglandin F2?, not a human heart tissue sample since it is difficult to get human samples to do the experiment. Powel et al measured the serum of 57 patients with HCM and found significant increase in 8-Isoprostaglandin F2 ? as compared to the normal controls 35.4 ± 10.2 versus 29.9 ± 9.9 Pg/ml with the p value of <0.001. Though all patients had significant increase in oxidative stress than controls, the oxidative stress in those with left ventricular outflow obstruction were even higher than the non obstructive type ADDIN EN.CITE <EndNote><Cite><Author>Dimitrow</Author><Year>2009</Year><RecNum>38</RecNum><DisplayText>117</DisplayText><record><rec-number>38</rec-number><foreign-keys><key app=”EN” db-id=”0z9efa5ex2wd9re9s9tx992m99zfteaszxaz” timestamp=”1519294046″>38</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Dimitrow, P. P.</author><author>Undas, A.</author><author>Wolkow, P.</author><author>Tracz, W.</author><author>Dubiel, J. S.</author></authors></contributors><auth-address>2nd Department of Cardiology, Collegium Medicum, Jagiellonian University, Kopernika 17, PL 31-501 Krakow, Poland. [email protected]</auth-address><titles><title>Enhanced oxidative stress in hypertrophic cardiomyopathy</title><secondary-title>Pharmacol Rep</secondary-title><alt-title>Pharmacological reports : PR</alt-title></titles><periodical><full-title>Pharmacol Rep</full-title><abbr-1>Pharmacological reports : PR</abbr-1></periodical><alt-periodical><full-title>Pharmacol Rep</full-title><abbr-1>Pharmacological reports : PR</abbr-1></alt-periodical><pages>491-5</pages><volume>61</volume><number>3</number><keywords><keyword>Cardiomyopathy, Hypertrophic/*blood/complications/diagnostic imaging/pathology</keyword><keyword>Cohort Studies</keyword><keyword>Dinoprost/*analogs &amp; derivatives/blood</keyword><keyword>Echocardiography</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Oxidative Stress</keyword><keyword>Ventricular Outflow Obstruction/*blood/complications/diagnostic imaging/pathology</keyword></keywords><dates><year>2009</year><pub-dates><date>May-Jun</date></pub-dates></dates><isbn>1734-1140 (Print) 1734-1140 (Linking)</isbn><accession-num>19605948</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19605948</url></related-urls></urls></record></Cite></EndNote>117. Our three patients had non-obstructive type of HCM and they had also significant increase in oxidative stress. A close related study was the one that was done by Nakamura et al, where they used Endomyocardial biopsy samples obtained through internal jugular venous approach where the samples were taken on the right ventricular side of the septum. In this study they measured the amount of Oxidative stress in patients with HCM by measuring the amount of 4-hydroxy-2-nonenol (HNE) from the biopsy samples. HNE is an aldehyde obtained as a final product in the lipid peroxidation of lipid cell membranes done by ROS. 31 patients were involved in the study and these patients had left ventricular systolic dysfunction. Significantly high levels of HNE expression was found in patients with HCM compared to the control group (16,753 ± 10,723 in those with HCM versus 3548 ± 2574 ?m2 in the control group with the P value of 0.0005). The levels were even higher in patients with systolic dysfunction compared to both obstructive and non-obstructive group 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 118. Left ventricular systolic dysfunction HCM is the rare group of patients comprising 10-15% of patients with HCM 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 ADDIN EN.CITE 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ADDIN EN.CITE.DATA 118, in our study patient 3 had left ventricular systolic dysfunction with the ejection fraction of 17%. The study by Nakamura et al was meant to find the possible enhancement of oxidative stress in patients with HCM and systolic dysfunction compared to the one with diastolic dysfunction HCM and the relationship between systolic dysfunction and the level of oxidative stress. In their study, different results were obtained since all the hearts had increased oxidative stress compared to the normal and no heart had superior results compared to the other two. According to the study done by Nakamura et al, the hearts of patients with systolic dysfunction had higher oxidative stress compared to the one without it, which made them to conclude oxidative stress to be a cause for systolic heart failure. According to our study, all the hearts had proportional increase in ROS as the heart with systolic heart failure had higher ROS in some chambers compared to other hearts but again less ROS in other chambers compared to the others. So no one heart was superior to the other in terms of amount of ROS. This should not totally negate the concept concluded by Nakamura et al because the effect might have been caused by the very small number of sample size we were working on. Further research with large sample size could be useful. Myocardial hypertrophy, interstitial fibrosis and myofibrillar disarray in HCM are normally seen in the lower chambers more than the upper ones. The left ventricle is normally affected more than the right one specifically in its inter-ventricular septum. Since ROS is implicated in causing the cardiac phenotypes present in HCM, then it is expected to be seen more in the lower chambers specifically the left ventricle in its inter-ventricular septum followed by the right ventricle and the upper chambers being the last. Our study supports this as the lower chambers had significantly higher ROS compared to the upper ones. In the first heart sample and the third heart sample, the left ventricle had significantly higher oxidative stress followed by the inter-ventricular septum and then the right ventricle and lastly the upper chambers. For the second heart, the inter-ventricular septum had significantly higher oxidative stress than the left ventricle, which was followed by the right ventricle and ended up with the upper chambers. The inter-ventricular septum had higher oxidative stress probably because it was the inter-ventricular side of the left ventricle while in the first heart and the third heart; the inter-ventricular septum had right ventricular side of origin.From the analysis of this study, there is significantly higher reactive oxygen species in the hearts with HCM compared to the normal hearts. The ROS is higher in the lower chambers than the upper chambers where the left ventricle is affected more than the right one especially in its inter-ventricular septum. The hearts with Systolic dysfunction HCM have higher oxidative stress compared to the ones with diastolic dysfunction though all have increase in the amount of ROS.5.1. LIMITATION AND STREGHTH OF THE STUDYThe major limitation of this study was limited number of samples. Getting a sample of human heart have been very difficult and takes a long time.Not only that but also we were able to work on only three chambers of the heart, this is because the left atrium was never provided so the oxidative stress status of the left atrium remain to be unknown. There was only one normal heart sample which was compared with the rest of the diseased heart samples and the normal heart sample was the right atrium a chamber which is not affected much by oxidative stress as we have discussed above. A control of the left ventricle would have been the best control as it is the chamber which is affected most in HCM.CHAPTER 6: CONCLUSIONHypertrophic cardiomyopathy is one of the devastating diseases due to its risk of sudden cardiac death and the risk of heart failure. As from our study and many other, oxidative stress have shown a significant role of its involvement in the phenotypic expression of the disease as it cause destruction of the heart muscles and weaken them in various ways mostly important its ability to activate various signaling pathways to cause the phenotypes present in the HCM. Antioxidants would play a great role reversing the phenotype present in the disease and even preventing the occurrence of the phenotype for the genetically affected individuals as not all the genetic carriers do express the disease which gives even more hope. 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