Molecular Defects in Cardiovascular Disease978-1-4419-7130... · 2017-08-27 · become defective and are thus associated with the genesis of cardiovascular dysfunction in different

Molecular Defects in Cardiovascular Disease

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Naranjan S. Dhalla • Makoto Nagano Bohuslav OstadalEditors

Molecular Defects in Cardiovascular Disease

EditorsNaranjan S. Dhalla, PhD, MD (Hon)Institute of Cardiovascular SciencesSt. Boniface General Hospital Research Centre Winnipeg, Canadaand Department of Physiology Faculty of Medicine University of Manitoba Winnipeg, [email protected]

Bohuslav Ostadal, MD, DScCentre for Cardiovascular ResearchAcademy of Sciences of the Czech RepublicPrague, Czech Republicand Institute of Physiology Academy of Sciences of the Czech Republic Prague, Czech [email protected]

Makoto Nagano, MD, PhDJikei University School of MedicineTokyo, [email protected]

ISBN 978-1-4419-7129-6 e-ISBN 978-1-4419-7130-2DOI 10.1007/978-1-4419-7130-2Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2011933568

© Springer Science+Business Media, LLC 2011All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

This book is dedicated in the memory of Kalwant (Ken) S. Dhalla for his untiring efforts to serve the cardiovascular community throughout the world during 1977–2010. This tribute to Ken Dhalla is accorded for his special talents in promoting collaborations and friendships within members of the International Society for Heart Research and the International Academy of Cardiovascular Sciences. Ken was a scholar, philosopher, and a great human being. His positive approach to see goodness in everybody and every event are truly being missed.

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Preface

Cardiovascular disease is a major challenge for the health care system as it encompasses high levels of mortality and morbidity. Various cardiovascular complications, such as atherosclerosis, hypertension, and diabetes, are known to predispose the heart to become more susceptible to myocardial infarction and/or other pathological stimuli leading to the development of congestive heart failure. Not only is the cardiac muscle adversely affected, but also differ-ent risk factors are known to directly result in severe vascular abnormalities. It is generally considered that there occurs hormonal imbalance at initial stages of heart disease, and this results in the occurrence of some adaptive changes, including cardiac hypertrophy, for maintaining the normal status of the cardiovascular system. However, prolonged exposure of the body to diverse pathological stimuli ends up in the malfunction of cardiac and vascu-lar myocytes. Despite a great deal of efforts, which have been made over the past 60 years, no satisfactory cure is available for the treatment of cardiovas-cular dysfunction associated with different types of heart disease. This state of affairs is primarily due to the lack of our knowledge concerning the mecha-nisms leading to cardiovascular dysfunction as well as the identification of specific targets for drug development and therapy. This problem is further complicated by the fact that cardiovascular defects are now being recognized as dependent upon the type as well as stage of the disease.

Recently, numerous studies are being directed for understanding the process of remodeling of cardiomyocytes and vascular myocytes to uncover the molecular mechanisms of cardiovascular dysfunction. In particular, vari-ous signal transduction systems, which affect the genetic machinery of the cell, are being explored in both cardiovascular health and disease. It is becoming clear that the occurrence of oxidative stress and the development of intra cellular Ca2+-overload, as well as metabolic derangements, play an important role in the activation of different proteases and phospholipases for the inhibition of subcellular organelle function. Furthermore, these mecha-nisms have also been discovered to alter the gene expression in both cardio-myocytes and vascular myocytes, and thus affect subcellular remodeling and activities of subcellular organelles. In particular, the functional groups of proteins in subcellular organelles become inactivated and/or protein con-tent of different subcellular organelles, including sarcolemma, sarcoplasmic

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reticulum, mitochondria, myofibrils, and nucleus, as well as extracellular matrix become altered. These changes are then considered to result in abnor-malities of cardiovascular function. The present book was, therefore, assem-bled to emphasize the significance of various molecular mechanisms which become defective and are thus associated with the genesis of cardiovascular dysfunction in different types of heart disease.

This book on “Molecular Defects in Cardiovascular Disease” is based on 27 invited articles from well-known investigators with distinct expertise in their fields of cardiovascular sciences. These articles have been arranged in three sections, namely: (a) Molecular Mechanisms in Heart Disease, (b) Cardiac Hypertrophy and Heart Failure, and (c) Hypertension and Diabetes. The first section is focused on general discussion for the role of intracellular Ca2+-overload, oxidative stress, metalloproteases, regulation of intracellular elec-trolytes, hypoxic injury, and cell therapy for cardioprotection to emphasize the role of changes in molecular mechanisms for the development of cardio-vascular dysfunction. The second section deals with metabolic derangements, Ca2+-handling, and subcellular remodeling during the development of cardiac hypertrophy and heart failure with or without drug treatments. This section illustrates the role of a wide variety of molecular defects which may serve as targets associated with the transition of cardiac hypertrophy to heart failure. The third section in this book is mainly concerned with vascular defects which are associated with hypertension and diabetes. In addition, the impor-tance of different hormones in the pathogenesis of hypertension and diabetic cardiomyopathy has been highlighted. Thus, the information outlined in this book can be seen to provide a multifaceted approach to find solutions of prob-lems associated with cardiovascular dysfunction.

We are indeed grateful to Mrs. Eva Little and Dr. Vijayan Elimban for their help in the preparation of manuscripts for editing purposes. Our thanks are also due to Ms. Frances Louie and Mr. Ian Hayes, Springer New York, for their advice during the editorial process. It is hoped that this book containing state of the art articles will be valuable to students, fellows, scientists, clini-cians, and surgeons for gaining insight into the molecular mechanisms of cardiovascular disease.

Winnipeg, Canada Naranjan S. DhallaTokyo, Japan Makoto NaganoPrague, Czech Republic Bohuslav Ostadal

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Contents

Part I Molecular Mechanisms in Heart Disease

Calcium Overloading-Induced Oxidative Stress-Mediated Cellular and Subcellular Remodeling .................. 3Yaser Cheema, Atta U. Shahbaz, Syamal K. Bhattacharya, Robert A. Ahokas, Yao Sun, Ivan C. Gerling, and Karl T. Weber

Intracellular MMP-2: Role in Normal and Diseased Hearts ............................................................................ 17Nermeen Youssef and Richard Schulz

Control of the Mesenchymal-Derived Cell Phenotype by Ski and Meox2: A Putative Mechanism for Postdevelopmental Phenoconversion ........................................... 29Ryan H. Cunnington, Josette M. Douville, Jeffrey T. Wigle, Darren H. Freed, Dedmer Schaafsma, Sarah O’Connor, Shivika Gupta, Sunil G. Rattan, Andrew J. Halayko, and Ian M.C. Dixon

Elevated Na+–H+ Exchanger Expression and Its Role in Myocardial Disease ......................................................................... 43Larry Fliegel

Impact of Perinatal Chronic Hypoxia on Cardiac Tolerance to Acute Ischemia .............................................................. 55Bohuslav Ostadal, I. Ostadalova, F. Kolar, I. Netuka, and O. Szarszoi

Stem Cell, MicroRNA and Redox Cycling ........................................ 69Partha Mukhopadhyay, Narasimman Gurusamy, and Dipak K. Das

Cardiac Cell Therapy: Present and Future ...................................... 83Dinender K. Singla

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Part II Cardiac Hypertrophy and Heart Failure

Macroscopic and Microscopic Aspects of Cardiac Dysfunction in Congestive Heart Failure .......................................... 95Henk E.D.J. ter Keurs

Cardiac Dysfunction and Metabolism: Unravelling the Molecular Cross-Talk ................................................................... 109Vijay Sharma and John H. McNeill

Metabolic Remodelling of the Hypertrophied Heart ....................... 127Jiazhen M. Dai and Michael F. Allard

Mechanisms for the Regulation of Phospholipase C Gene Expression in Cardiac Hypertrophy.................................... 141Paramjit S. Tappia

Molecular Changes in Fatty Acid Oxidation in the Failing Heart ........................................................................................ 153Jagdip S. Jaswal, Wendy Keung, Wei Wang, John R. Ussher, and Gary D. Lopaschuk

Cardiolipin Metabolism in Experimental and Human Heart Failure ....................................................................................... 177Grant M. Hatch

Mechanisms Underlying Development of Cardiomyocyte Hypertrophy via Na–H Exchange Stimulation ................................ 185Morris Karmazyn

The Structural Basis of Cardiac Dysfunction in Human Heart Failure ..................................................................... 197Stefan Hein, Sawa Kostin, and Jutta Schaper

Hormonal Mechanisms of Cardiac Remodeling in Heart Failure ................................................................................... 215Andrea P. Babick, Vijayan Elimban, and Naranjan S. Dhalla

Modulators of Remodeling After Myocardial Infarction ................ 231Bodh I. Jugdutt

Phosphodiesterase-5 Inhibitors in Protection Against Doxorubicin-Induced Cardiomyopathy .............................. 243Saisudha Koka and Rakesh C. Kukreja

Part III Hypertension and Diabetes

Molecular Basis of Pulmonary Hypertension in Left Heart Failure ........................................................................... 259Binil Raj, Harikrishnan Sivadasanpillai, and Chandrasekharan Cheranellore Kartha

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Modulation of Gi Protein Expression in Hypertension: Molecular Mechanisms ....................................................................... 273Madhu B. Anand-Srivastava

Vascular Dysfunction in Heart Disease ............................................. 283Raissa Perrault and Peter Zahradka

Cellular and Molecular Mechanisms Associated with Salicylate Inhibition of Intimal Hyperplasia Following Balloon Catheter-Induced Vascular Injury .................... 305S.N. Murthy, P.J. Kadowitz, and D.B. McNamara

Involvement of Growth Factor Receptor and Nonreceptor Protein Tyrosine Kinases in Endothelin-1 and Angiotensin II-Induced Signaling Pathways in the Cardiovascular System ...... 315George Vardatsikos and Ashok K. Srivastava

Sarco/Endoplasmic Reticulum Ca2+ Pump Damage by Oxidative Stress: Implications for Ca2+ Entry............................. 335Gauri Akolkar and Ashok K. Grover

Obesity–Hypertension: Leptin as the Common Link to Cardiovascular and Renal Dysregulation .................................... 343Shilpa Kshatriya, Hani Kozman, Danish Siddiqui, Luna Bhatta, Kan Liu, Ali Salah, Timothy Ford, Robert Michiel, Robert Carhart, and Daniel Villarreal

Cardiorenal Protection in Diabetes Mellitus .................................... 353Himanshu Vashistha, Leonard G. Meggs, and Ashwani Malhotra

Molecular Mechanisms in the Pathogenesis of Diabetic Cardiomyopathy .................................................................................. 365Subrata Chakrabarti

Index ..................................................................................................... 379

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Contributors

Robert A. Ahokas Department of Obstetrics & Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA

Gauri Akolkar Department of Biology, McMaster University, Hamilton, ON, Canada

Michael F. Allard Department of Pathology and Laboratory Medicine/James Hogg Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

Madhu B. Anand-Srivastava Department of Physiology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada

Andrea P. Babick Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Canada

Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

Luna Bhatta Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA

Veterans Affairs Medical Center, Syracuse, NY, USA

Syamal K. Bhattacharya Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

Robert Carhart Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA

Subrata Chakrabarti Department of Pathology, University of Western Ontario, London, Ontario, Canada

Yaser Cheema Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

xiv Contributors

Ryan H. Cunnington Department of Physiology, University of Manitoba and the Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

Jiazhen M. Dai Department of Pathology and Laboratory Medicine/Heart and Lung Institute, University of British Columbia, Vancouver, BC, Canada

Dipak K. Das Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT, USA

Naranjan S. Dhalla Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada


Ian M.C. Dixon Department of Physiology, University of Manitoba and the Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

Josette M. Douville Department of Biochemistry and Medical Genetics, University of Manitoba and the Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

Vijayan Elimban Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Canada


Larry Fliegel Department of Biochemistry, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada

Timothy Ford Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA


Darren H. Freed Department of Surgery, Section of Cardiac Surgery, University of Manitoba, Winnipeg, MB, Canada

Department of Physiology, University of Manitoba, Winnipeg, MB, Canada

The Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

Ivan C. Gerling Division of Endocrinology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

Ashok K. Grover Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Department of Biology, McMaster University, Hamilton, Ontario, Canada

Shivika Gupta Department of Physiology, University of Manitoba, Winnipeg, MB, Canada

xvContributors


Narasimman Gurusamy Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT, USA

Andrew J. Halayko Departments of Internal Medicine and Physiology, University of Manitoba, Winnipeg, MB, Canada

The Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, MB, Canada

Grant M. Hatch Department of Pharmacology and Therapeutics, Biochemistry and Medical Genetics, Internal Medicine, Faculty of Medicine, Center for Research and Treatment of Atherosclerosis, Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Canada

Stefan Hein Department of Cardiac Surgery, Kerckhoff Clinic, Bad Nauheim, Germany

Jagdip S. Jaswal Departments of Pediatrics and Pharmacology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada

Bodh I. Jugdutt Division of Cardiology, Department of Medicine, University of Alberta and Hospitals, Edmonton, Alberta, Canada

P.J. Kadowitz Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA

Morris Karmazyn Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada

Chandrasekharan Cheranellore Kartha Division of Cardiovascular Disease Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, India

Wendy Keung Departments of Pediatrics and Pharmacology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada

Henk E.D.J. ter Keurs Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada

Saisudha Koka Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, VA, USA

F. Kolar Centre for Cardiovascular Research, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

xvi Contributors

Sawa Kostin Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany

Hani Kozman Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA


Shilpa Kshatriya Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA

Rakesh C. Kukreja Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, VA, USA

Kan Liu Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA


Gary D. Lopaschuk Departments of Pediatrics and Pharmacology, University of Alberta, Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada

Ashwani Malhotra Division of Nephrology, Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY, USA

D.B. McNamara Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA

John H. McNeill Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada

Leonard G. Meggs Department of Nephrology, Ochsner Clinic Foundation, New Orleans, LA, USA

Robert Michiel Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA


Partha Mukhopadhyay Laboratory of Physiologic Studies, NIAAA, National Institute of Health, Bethesda, MD, USA

S.N. Murthy Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA

I. Netuka Centre for Cardiovascular Research, Prague, Czech Republic

Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Sarah O’Connor Department of Physiology, University of Manitoba and the Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

Bohuslav Ostadal Centre for Cardiovascular Research, Prague, Czech Republic


xviiContributors

I. Ostadalova Centre for Cardiovascular Research, Academy of Sciences of the Czech Republic, Prague, Czech Republic


Raissa Perrault Department of Physiology, University of Manitoba and Canadian Centre for Agrifood Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada

Harikrishnan Sivadasanpillai Department of Cardiology, Sree Chitra Tirunal Institute for Medical Science and Technology, Trivandrum, India

Binil Raj Division of Cardiovascular Disease Biology, Rajiv Gandhi Center for Biotechnology, Trivandrum, India

Sunil G. Rattan Department of Physiology, University of Manitoba, Winnipeg, MB, Canada


Ali Salah Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA


Dedmer Schaafsma Departments of Internal Medicine and Physiology, University of Manitoba, Winnipeg, MB, Canada

The Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, MB, Canada

Jutta Schaper Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany

Richard Schulz Departments of Pediatrics and Pharmacology, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada

Atta U. Shahbaz Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

Vijay Sharma Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada

Danish Siddiqui Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA


Dinender K. Singla Biomolecular Science Center, University of Central Florida, Orlando, FL, USA

xviii Contributors

Ashok K. Srivastava Laboratory of Cellular Signaling, Montreal Diabetes Research Center, Research Center – Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada

Department of Medicine, Université de Montréal, Montreal, Québec, Canada

Yao Sun Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

O. Szarszoi Centre for Cardiovascular Research, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Paramjit S. Tappia Asper Clinical Research Institute, St. Boniface Hospital Research and Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada

John R. Ussher Departments of Pediatrics and Pharmacology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada

George Vardatsikos Laboratory of Cellular Signaling, Montreal Diabetes Research Center, Research Center – Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, Québec, Canada

Department of Medicine, Université de Montréal, Montreal, Québec, Canada

Himanshu Vashistha Department of Nephrology, Ochsner Clinic Foundation, New Orleans, LA, USA

Daniel Villarreal Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA


Wei Wang Departments of Pediatrics and Pharmacology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada

Karl T. Weber Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

Jeffrey T. Wigle Department of Biochemistry and Medical Genetics, University of Manitoba and the Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada

Nermeen Youssef Departments of Pediatrics and Pharmacology, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada

Peter Zahradka Department of Physiology, University of Manitoba and Canadian Centre for Agrifood Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada

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Molecular Defects in Cardiovascular Disease978-1-4419-7130... · 2017-08-27 · become defective and are thus associated with the genesis of cardiovascular dysfunction in different