HEART HYPERTROPHY AND FAILURE

DEVELOPMENTS IN CARDIOVASCULAR MEDICINE

121. S. Sideman, R. Beyar and A.G. Kleber (eds): Cardiac Electrophysiology, Circulation, and Transport. Proceedings of the 7th Henry Goldberg Workshop (Berne, Switzerland, 1990). 1991. ISBN 0-7923-1145-0.

122. D.M. Bers: Excitation-Contraction Coupling and Cardiac Contractile Force. 1991. ISBN 0-7923-1186-8.

123. A.-M. Salmasi and A.N. Nicolaides (eds): Occult Atherosclerotic Disease. Diagnosis, Assessment and Management. 1991. ISBN 0-7923-1188-4.

124. JA.E. Spaan: Coronary Blood Flow. Mechanics, Distribution, and Control. 1991. ISBN 0-7923-1210-4.

125. R.W. Stout (ed): Diabetes and Atherosclerosis. 1991. ISBN 0-7923-1310-0. 126. A.G. Herman (ed): Antithrombotics. Pathophysiological Rationale for Pharmacological

Interventions. 1991. ISBN 0-7923-1413-1. 127. N. H.J. Pijls: Maximal Myocardial Perfusion as a Measure of the Functional Significance of

Coronary Arteriogram. From a Pathoanatomic to a Pathophysiologic Interpretation of the Coronary Arteriogram. 1991. ISBN 0-7923-1430-1.

128. JH.C. Reiber and E.E. v.d. Wall (cds): Cardiovascular Nuclear Medicine and MRI. Quantitation and Clinical Applications. 1992. ISBN 0-7923-1467-0.

129. E. Andries, P. Brugada and R. Stroobrandt (eds): How to Face "the Faces" of Cardiac Pacing. 1992. ISBN 0-7923-1528-6.

130. M. Nagano, S. Mochizuki and N.S. Dhalla (eds): Cardiovascular Disease in Diabetes. 1992. ISBN 0-7923-1554-5.

131. P. W. Serruys, B.H. Strauss and S.B. King III (cds): Restenosis after Intervention with New Mechanical Devices. 1992. ISBN 0-7923-1555-3.

132. P.J. Walter (cd): Quality of Life after Open Heart Surgery. 1992. ISBN 0-7923-1580-4. 133. E.E. van der Wall, H. Sochor, A. Righetti and M.G. Niemeyer (cds): What is new in

Cardiac Imaging? SPECT, PET and MRI. 1992. ISBN 0-7923-1615-0. 134. P. Hanrath, R. Uebis and W. Krebs (cds); Cardiovascular Imaging by Ultrasound. 1992.

ISBN 0-7923-1755-6. 135. F.H. Messerli (cd): Cardiovascular Disease in the Elderly, 3rd cd. 1<)<)2. ISBN 0-7923-1859-

5. 136. J. Hess and G.R. Sutherland (eds): Congenital Heart Disease in Adolescents and Adults.

1992. ISBN 0-7923-1862-5. 137. JH.C. Reiber and P. W. Serruys (cds): Advances in Quantitative Coronary Arteriography.

1993. ISBN 0-7923-1863-3. 138. A.-M. Salmasi and AS Iskandrian (cds): Cardiac Output and Regional Flow in Health and

Disease. 1993. ISBN 0-7923-1911-7. 139. JH. Kingma, N.M van Hemel and K.l. Lie (eds): Atrial Fibrillation, a Treatable Disease'

1992. ISBN 0-7923-2008-5. 140. B. Ostadal, N.S. Dhalla (cds): Heart Function in Health and Disease. 1993. ISBN 0-7923-

2052-2. 141. D. Noble and Y.E. Earm (eds): IOllic Challlle/s and Effect ~r Taurine on the Heart. Proceedings

of an International Symposium (Seoul, Korea, 1992). 1993. ISBN 0-7923-2199-5. 142. H.M. Piper and C.J. Preusse (eds): Ischemia-reperfusion in Cardiac Surgery. 1993. ISBN 0-

7923-2241-X. 143. J Roelandt, E.J. Gussenhoven and N. Born (cds): Intravascular Ultrasound. 1993. IBN 0-

7923-2301-7. 144. M.E. Safar and M.F. O'Rourke (cds): The Arterial System in Hypertensioll. 1993. ISBN 0-

7923-2343-2. 145. P.W. Serruys, D.P. Foley and P.J. de Feyter (cds): Qualltitative Corolwry AllgioJ?raphy ill

Clillical Practice. 1993. ISBN 0-7923-2368-8. 146. J Can dell-Riera and D. Ortega-Alcalde (eds): Nuclear Cardiology ill Everyday Practice. 1993.

ISBN 0-7923-2374-2. 147. P. Cummins (ed): Growth Factors alld the Cardiovascular System. 1993. ISBN 7923-2401-3. 148. K. Przyklenk, R.A. Kloner and D.M. Yellon (cds): Ischemic Precollditioning: The CO/lCept oj

Endogenous Cardioprotectioll. 1993. ISBN 0-7923-2410-2.

HEART HYPERTROPHY AND FAILURE

Edited by NARANJAN S. DHALLA Distinguished Professor

GRANT N. PIERCE Professor

VINCENZO PANAGIA Professor

ROBERT E. BEAMISH Professor Emeritus

MRC Group in Experimental Cardiology Division of Cardiovascular Sciences SI. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba Winnipeg, Manitoba, Cmzada

~.

" KLUWER ACADEMIC PUBLISHERS

BOSTON IDORDRECHT ILONDON

Distributors for North America: Kluwer Academic Puhlishers 101 Philip Drive Assinippi Park Norwell, Massachusetts 02061 USA

Distributors for all other countries: Kluwer Academic Puhlishers Group Distribution Centre Post Office Box 322 3300 AH Dordrecht, THE NETHERLANDS

Library of Congress Cataloging-in-Publication Data A CI.P. Catalogue record for this book is available from the Library of Congress.

ISBN-13: 978-1-4612-8526-7 DOl: 10.1007/978-1-4613-1237-6

e-ISBN-13: 978-1-4613-1237-6

Copyright © 1995 by Kluwer Academic Publishers

Softcover reprint of the hardcover 1st edition 1995

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photo-copying, recording, or otherwise, without the prior written permission of the publisher, Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, Massachusetts 02061

Printed on acid-free paper.

Henry G. Friesen, M.D., Ottawa, Canada

This book is dedicated to Dr. Henry G. Friesen, President, Medical Research

Council of Canada, for his untiring efforts in the promotion of health

research In general and cardiovascular research in particular throughout

Canada. The Division of Cardiovascular Sciences at the St. Boniface General

Hospital Research Centre is indebted to Dr. Friesen for his enthusiastic

support, advice, and leadership, which he provided during his tenure at the

University of Manitoba.

CONTENTS

List of contributors Xl

Preface xxxv

Acknowledgments XXXVll

A. GENETIC AND MOLECULAR EVENTS

1. Molecular analysis of genotype/phenotype correlations of hypertrophic cardiomyopathy 3 ROBERT ROBERTS, LINDA BACHINSKI, QUN-TAO YU, MIGUEL QUINONES,

ROBERT YOUNG, and ALI J. MARIAN

2. Molecular genetics: New mutations that cause familial hypertrophic cardiomyopathy 21 CALUM A. MACRAE, LUDWIG H. THEIRFELDER, HUGH C. WATKINS, RYUCHIRO ANAN,

J.G. SEIDMAN, and CHRISTINE E. SEIDMAN

3. Genetically determined cardiomyopathies in neuromuscular disease 27

KLAUS WROGEMANN

4. Mitochondrial DNA mutations and heart failure 39 TAKA YUKI OZAWA, KAZUMI KATSUMATA, MIKA HAYAKAWA, MAKOTO YONEDA,

MASASHI TANAKA, and SATORU SUGIYAMA

5. Mutations of myocardial mitochondrial DNA in diabetic patients 59 NOBUAKIRA TAKEDA, AKIRA TANAMURA, TAKAAKI IWAI, YUUSAKU HAYASHI, and SATOKO NOMURA

viii Contents

6. Differential screening and mega sequencing of human heart eDNA library: A search for genes associated with heart failure 67

CHOONG-CHIN LIEW, RUOXIANG WANG, EVA CUKERMAN, and BAOSHENG CHEN

7. Intracellular signaling and genetic reprogramming during development of hypertrophy in cultured cardiomyocytes 79 HAN A.A. VAN HEUGTEN, HENRIETTE W. DE JONGE, MIRIAM A. GOEDBLOED,

KAREL BEZSTAROSTI, HARI S. SHARMA, PIETER D. VERDOUW, and JOS M.J. LAMERS

8. Phenotypic changes in experimental cardiac hypertrophy and failure in rclation to changes in heart rate variability 93 BERNARD SWYNGHEDAUW, FRANt;OIS CARRE, PASCALE MANSIER, BRIGITTE CHEVALIER,

CHRISTOPHE HEYMES, NATHALIE CHARLOTTE, JEAN-MARIEC MOALIC, and DANIELE CHARLEMAGNE

9. Relationship between myocardial function and expression of calcium cycling proteins in nonfailing and failing human myocardium 103

GERD HASENFUSS, HANS REINECKE, ROLAND STUDER, BURKERT PIESKE, MARKUS MEYER,

JURGEN HOLTZ, CHRISTIAN HOLUBARSCH, HELMUT DREXLER, and HANJORG JUST

10. Cardiac remodeling by alterations in phospholamban protein levels 117

WUSHENG LUO, EVA KISS, KIMBERLY L. KOSS, INGRID I.. GRUPP, JUDY M. HARRER,

W. KEITH JONES, ISTVAN EDES, and EVANGELIA G. KRANIAS

11. Regulation of sarcoplasmic reticulum gene expression during cardiac hypertrophy and heart failure 139

DEBRA BAKER, MASASHI ARAI, HIRO MATSUI, DREW SUKOVICH, JUNAID SHABBEER,

VRUSHANK DAVE, RICHARD A. WALSH, and MUTHU PERIASAMY

12. Hormonal regulation of cardiac sarcoplasmic reticulum Ca2+ -ATPase expression 155 ANGEL ZARAIN-HERZBERG

B. CELLULAR AND BIOCHEMICAL MECHANISMS

13. Growth of the neonatal pig heart 171 CA THY J. BEINLICH and HOWARD E. MORGAN

14. Regulation of cardiac myocyte differentiation, hyperplasia, and hypertrophy during normal and stressed fetal and neonatal growth 183

SANFORD P. BISHOP

15. Rat heterotopic cardiac isograft model: What atrophy teaches us about hypertrophy 197

PETER M. BUTTRICK, DAVID I.. GEENEN, ASHWANI MALHOTRA, and JAMES SCHEUER

16. Myocardial cell abnormalities in heart failure: Experience from studies on single myocytes 205 CRISPIN H. DAVIES, LESLEY A. BROWN, FEDERICA DEL MONTE,

PHILIP A. POOLE-WILSON, and SIAN E. HARDING

17. Depression of sarcolemmal phospholipase C activity in congestive heart failure 221 VINCENZO PANAGIA, JOHANNA T.A. MEIJ, NASRIN MESAELI, ROHIT K. SINGAL,

and NARANJAN s. DHALLA

Contents ix

18. Docs decreased energy supply contribute to heart failure? The role of the creatine kinase system 231

JOANNE S. INGWALL, JAN FRIEDRICH, and LUIGINO NASCIMBEN

19. Molecular basis for depressed contractile performance in human heart failure 241

NORMAN R. ALPERT, LOUIS A. MULIERI, and GERD HASENFUSS

20. Cellular adaptations in hypertrophy and heart failure 257 K.G. NAIR

21. Progressive ventricular dilatation in heart failure: The role of myocardial collagenase 261 JOSEPH S. JANICKI, SURESH C. TYAGI, SCOTT E. CAMPBELL,

HANUMANTH K. REDDY, and JEFFREY R. HENEGAR

22. Interaction between cardiac myocytes and the extracellular matrix in failing human myocardium 275

JUTTA SCHAPER, HANKE MOLLNAU, STEFAN HEIN, and BRIGITTE MUNKEL

23. Role of transforming growth factor betal in the remodeling of collagen matrix in the heart 287 MAHBOUBEH EGHBALI-WEBB and ANDREAS SIGEL

24. Cytokines modulate the expression of specific proteins of the contractile apparatus in rat myocytes 299

STIG HAUNS0, STEPHEN J. FEY, GITTE STAWSKI, ULLA ANDRUP JENSEN,

J0RN CARLSEN, PETER RIIS HANSEN, and PETER MOSE LARSEN

C. SIGNAL TRANSDUCTION ABNORMALITIES

25. Rethinking ras: p21 ras proteins and cardiac signal transduction 311 MAHA ABDELLATIF and MICHAEL D. SCHNEIDER

26. Regulation of uMHC gene expression by cAMP 333 MAHESH P. GUPTA, MADHU GUPTA, and RADOVAN ZAK

27. Cardiac hypertrophy and the renin-angiotensin system 347 YOSHIO YAZAKI, ISSEI KOMURO, TSUTOMU YAMAZAKI, ICHIRO SHIOJIMA, and RYOZO NAGAI

28. Stimulation of p-adrenoceptor subtypes causes different effects in cardiac cells 359 RUI-PING XIAO and EDWARD G. LAKATTA

29. Significance of adrenergic stimuli for cardiac remodeling under chronic overload: Relative importance of myocardial factors versus ventricular geometry in cardiac failure 381 MARIAN BRANDLE, BERNHARD DIERBERGER, GERHARD MALL, and RUTHARDJACOB

30. Sympathetic neuroeffector mechanisms in the failing and hypertrophied myocardium 403 MICHAEL BOHM

x Contents

31. Status of post adrenergic receptor mechanisms in cardiac hypertrophy and heart failure 419

RAJAT SETHI, KEN S. DHALLA, VINCENZO PANAGIA, and NARANJAN s. DHALLA

32. Role of protein kinase C in the development of non -insulin-dependent diabetic cardiomyopathy 447

STEPHEN SCHAFFER, CHERRY BALLARD, and ARIN BHATTACHARJEE

33. The alteration of signal transduction system in heart failure: renin­angiotensin system in diseased human heart 463 HIDEAKI KAWAGUCHI and AKIRA KITABATAKE

34. Neuroendocrine mechanisms in the pathogenesis of heart failure 475

KURT KOCHSIEK

35. Neurohormonal responses in congestive heart failure: effect of ACE inhibitors in randomized controlled clinical trials 487 INDER S. ANAND and Y. CHANDRASHEKHAR

Subject index 503

LIST OF CONTRIBUTORS

Maha Abdellatif Molecular Cardiology Unit One Baylor Plaza, Room 506C Baylor College of Medicine Houston, TX 77030 USA

Norman R. Alpert Department of Molecular Physiology and Biophysics University of Vermont College of Medicine Burlington, VT 05405 USA

R yuchiro Anan Departments of Genetics and Cardiology Harvard Medical School 200 Longwood A venue Boston, MA 02115 USA

xii List of contributors

Inder S. Anand University of Minnesota Medical School V A Medical Center 1I1C One Veterans Drive Minneapolis, MN 55417 USA

Masashi Arai Gunma University School of Medicine Second Department of Internal Medicine Showa-Machi, Maebashi Gunma Japan

Linda Bachinski Division of Cardiology Baylor College of Medicine 6550 Fannin, MS SM677 Houston, TX 77030 USA

Debra Baker Molecular Cardiology Laboratory Division of Cardiology University of Cincinnati College of Medicine 231 Bethesda Avenue, P.O. Box 670542 Cincinnati, OH 45267 USA

Cherry Ballard University of South Alabama School of Medicine Department of Pharmacology MSB 3130 Mobile, AL 36688-0002 USA

Cathy J. Beinlich Weis Center for Research Geisinger Clinic Danville, P A 17822-2619 USA

Karel Bezstarosti Department of Biochemistry Cardiovascular Research Institute COEUR Faculty of Medicine and Health Sciences Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands

Arin Bhattacharjee University of South Alabama School of Medicine Department of Pharmacology MSB 3130 Mobile, AL 36688-0002 USA

Sanford P. Bishop Department of Pathology University of Alabama at Birmingham 1670 University Boulevard Birmingham, AL 35294-0019 USA

Michael Bahm Klinik III fUr Innere Medizin Universitat zu Kaln Joseph-Stelzmann Str. 9 50924 Kaln Germany

Marian Brandle Physiologisches Institut II Universitat Tiibingen Gmclinstraf3e 5 72076 Tiibingen Germany

Lesley A. Brown Department of Cardiac Medicine National Heart and Lung Institute Dovehouse Street London SW3 6L 7 United Kingdom

List of contributors xiii

xiv List of contributors

Peter M. Buttrick Division of Cardiology Montefiore Medical Center Albert Einstein College of Medicine 111 East 210th Street Bronx, NY 10467 USA

Scott E. Campbell Department of Internal Medicine and Dalton Cardiovascular Research Center University of Missouri One Hospital Drive Columbia, MO 65212 USA

J 0rn Carlsen Department of Medicine B, 2142 Rigshospitalet University of Copenhagen 9 Blegdamsvej DK-2100 Copenhagen 0 Denmark

Fran~ois Carre Department of Physiology Faculty of Medicine University of Rennes 2 avenue du Prof. Leon Bernard 35043 Rennes France

Y. Chandrashekar University of Minnesota Medical School V A Medical Center mc One Veterans Drive Minneapolis, MN 55417 USA

Daniele Charlemagne U 127-INSERM Hopital Lariboisiere 41 Bd de la Chapelle 75010 Paris France

Nathalie Charlotte U 127-INSERM Hopital Lariboisiere 41 Bd de la Chapelle 75010 Paris France

Baosheng Chen Institute of Basic Medical Sciences The Chinese Academy of Medical Science Beijing P.R. China

Brigitte Chevalier U 127-INSERM Hopital Lariboisicre 41 Bd de la Chapelle 75010 Paris France

Eva Cukerman Department of Clinical Biochemistry University of Toronto 100 College Street Toronto, ON M5G lL5 Canada

Vrushank Dave Molecular Cardiology Laboratory Division of Cardiology University of Cincinnati College of Medicine 231 Bethesda Avenue, P.O. Box 670542 Cincinnati, OH 45267 USA

Crispin H. Davies Department of Cardiac Medicine National Heart and Lung Institute Dovehouse Street London SW3 6L7 United Kingdom

List of contributors xv

xvi List of contributors

Henriette W. de J onge Department of Biochemistry Cardiovascular Research Institute COEUR Faculty of Medicine and Health Sciences Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands

Federica del Monte Department of Cardiac Medicine National Heart and Lung Institute Dovehouse Street London SW3 6L7 United Kingdom

Ken S. Dhalla Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre 351 Tache Avenue Winnipeg, MB R2H 2A6 Canada

Naranjan S. DhaJla Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre 351 Tache Avenue Winnipeg, MB R2H 2A6 Canada

Bernhard Dierberger Physiologisches Institut II Universitat Tiibingen Gmelinstra!3e 5 72076 Tiibingen Germany

Helmut Drexler Universitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg Germany

Istvan Edes Department of Pharmacology and Cell Biophysics University of Cincinnati College of Medicine P.O. Box 670575 Cincinnati, OH 45267-0575 USA

Mahboubeh Eghbali-Webb Department of Anesthesiology Yale University School of Medicine 333 Cedar Street P.O. Box 3333 New Haven, CT 06510 USA

Stephen J. Fey Institute for Medical Microbiology and Immunology The Bartholin Building University of Aarhus DK-8000 Aarhus C Denmark

J an Friedrich NMR Laboratory for Physiological Chemistry Department of Medicine Brigham & Women's Hospital 221 Longwood A venue Boston, MA 02115 USA

David L. Geenen Division of Cardiology Montefiore Medical Center Albert Einstein College of Medicine 111 East 210th Street Bronx, NY 10467 USA

Miriam A. Goedbloed Thoraxcentre Cardiovascular Research Institute COEUR Faculty of Medicine and Health Sciences Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands

List of contributors xvii

xviii List of contributors

Ingrid L. Grupp Department of Pharmacology and Cell Biophysics University of Cincinnati College of Medicine P.O. Box 670575 Cincinnati, OH 45267-0575 USA

Madhu Gupta Department of Medicine, MC 5105 University of Chicago 5841 S. Maryland Avenue Chicago, IL 60637 USA

Mahesh P. Gupta Department of Medicine, MC 5105 University of Chicago 5841 S. Maryland Avenue Chicago, IL 60637 USA

Peter Riis Hansen Department of Medicine B, 2142 Rigshospitalct University of Copenhagen 9 Blegdamsvej DK-2100 Copenhagen 0 Denmark

Sian E. Harding Department of Cardiac Medicine National Heart and Lung Institute Dovehouse Street London SW3 6L Y United Kingdom

Judy M. Harrer Department of Pharmacology and Cell Biophysics University of Cincinnati College of Medicine P.O. Box 670575 Cincinnati, OH 45267-0575 USA

Gerd Hasenfuss Universitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg Germany

Stig Hauns0 Department of Medicine B, 2142 Rigshos pita let University of Copenhagen 9 Blegdamsvej DK-2100 Copenhagen 0 Denmark

Mika Hayakawa Department of Biomedical Chemistry Faculty of Medicine University of Nagoya 65 Tsuruma-cho, Showa-ku Nagoya 466 Japan

Yuusaku Hayashi Department of Internal Medicine Aoto Hospital Jikei University School of Medicine Aoto 6-41-2, Katsushika-ku Tokyo 125 Japan

Stefan Hein Max-Planck-Institute Department of Experimental Cardiology Benekestrasse 2 D-61231 Bad Nauheim Germany

Jeffrey R. Henegar Department of Physiology and Pharmacology Auburn University Auburn, AL 36849-5519 USA

List of contributors xix

xx List of contributors

Christophe Heymes U 127-INSERM Hopital Lariboisiere 41 Bd de la Chapelle 75010 Paris France

Jiirgen Holtz Institut fiir Pathophysiologie Martin-Luther-Universitat Magdeburgerstrasse 6 06112 Halle/Saale Germany

Christian Holubarsch U niversitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg Germany

Joanne S. Ingwall NMR Laboratory for Physiological Chemistry Department of Medicine Brigham & Women's Hospital 221 Longwood Avenue Boston, MA 02115 USA

Takaaki Iwai Department of Internal Medicine Aoto Hospital Jikei University School of Medicine Aoto 6-41-2, Katsushika-ku Tokyo 125 Japan

Ruthard Jacob Physiologisches Institut II Universitat Tiibingen Gmelinstra~e 5 72076 Tiibingen Germany

Joseph S. Janicki Department of Physiology and Pharmacology 106 Greene Hall Auburn University Auburn, AL 36849-5519 USA

Ulla Andrup Jensen Institute for Medical Microbiology and Immunology The Bartholin Building Univesity of Aarhus DK-8000 Aarhus C Denmark

W. Keith Jones Department of Pharmacology and Cell Biophysics University of Cincinnati College of Medicine P.O. Box 670575 Cincinnati, OH 45267-0575 USA

Hanjorg Just U niversitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg, Germany

Kazumi Katsumata Department of Biomedical Chemistry Faculty of Medicine University of Nagoya 65 Tsuruma-cho, Showa-ku Nagoya 466 Japan

Hideaki Kawaguchi Department of Laboratory Medicine Hokkaido University School of Medicine Sapporo 060 Japan

List of contributors xxi

xxii List of contributors

Eva Kiss Department of Pharmacology and Cell Biophysics University of Cincinnati College of Medicine P.O. Box 670575 Cincinnati, OH 45267-0575 USA

Akira Kitabatake Department of Cardiovascular Medicine and Pathology Hokkaido University School of Medicine Sapporo 060 Japan

Kurt Kochsiek Department of Internal Medicine University of Wurzburg Josef-Schneider-Str. 2 D-97080 Wurzburg Germany

Issei Komuro Internal Medicine III University of Tokyo Tokyo 113 Japan

Kimberly L. Koss Department of Molecular and Cellular Physiology Univesity of Cincinnati College of Medicine Cincinnati, OH 45267 USA

Evangelia G. Kranias Department of Pharmacology and Cell Biophysics University of Cincinnati College of Medicine P.O. Box 670575 Cincinnati, OH 45267-0575 USA

Edward G. Lakatta Laboratory of Cardiovascular Science Gerontology Research Center 4940 Eastern A venue Baltimore, MD 21224 USA

Jos M.J. Lamers Department of Biochemistry Cardiovascular Research Institute COEUR Faculty of Medicine and Health Sciences Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands

Peter Mose Larsen Institute for Medical Microbiology and Immunology The Bartholin Building University of Aarhus DK-8000 Aarhus C Denmark

Choong-Chin Liew Department of Clinical Biochemistry University of Toronto 100 College Street Toronto, ON M5G 1L5 Canada

Wusheng Luo Department of Pharmacology and Cell Biophysics University of Cincinnati College of Medicine P.O. Box 670575 Cincinnati, OH 45267-0575 USA

Calum A. MacRae Departments of Genetics and Cardiology Harvard Medical School 200 Longwood A venue Boston, MA 02115 USA

Ashwani Malhotra Division of Cardiology Montefiore Medical Center Albert Einstein College of Medicine 111 East 210th Street Bronx, NY 10467 USA

List of contributors xxiii

xxiv List of contributors

Gerhard Mall Pathologisches Institut Stadtischc Krankenanstalten Grafenstra~e 9 64283 Darmstadt Germany

Pascale Mansier U 127-INSERM Hopital Lariboisiere 41 Bd de la Chapelle 75010 Paris France

Ali J. Marian Division of Cardiology Baylor College of Medicine 6550 Fannin, MS SM677 Houston, TX 77030 USA

Hiro Matsui Department of Bioclimatology Medical Institute of Bioregulation Kyushu University 4546 Tsuru Mibaru Beppu, Oita 874 Japan

Johanna T.A. Meij Department of Pharmacology University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75235-9041 USA

Nasrin Mesaeli Department of Biochemistry University of Alberta 417 Heritage Medical Research Centre Edmonton, AB T6G 2S2 Canada

Markus Meyer Universitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg Germany

Jean-Marie Moalic U 127-INSERM Hopital Lariboisiere 41 Bd de la Chapelle 75010 Paris France

Hanke Mollnau Max-Planck-Institute Department of Experimental Cardiology Benekestrasse 2 0-61231 Bad Nauheim Germany

Howard E. Morgan W cis Center for Research Geisinger Clinic Danville, P A 17822-2600 USA

Louis A. Mulieri Department of Molecular Physiology and Biophysics University of Vermont College of Medicine Burlington, VT 05405 USA

Brigitte Miinkcl Max-Planck-Institute Department of Experimental Cardiology Benekestrasse 2 0-61231 Bad Nauheim Germany

Ryozo Nagai Internal Medicine III University of Tokyo Tokyo 113 Japan

List of contributors xxv

xxvi List of contributors

K.G. Nair 206 Doctors House Opp. Jaslok Hospital Pedder Road Bombay 400 026 India

Luigino Nascimben NMR Laboratory for Physiological Chemistry Department of Medicine Brigham & Women's Hospital 221 Longwood Avenue Boston, MA 02115 USA

Satoko Nomura Department of Internal Medicine Aoto Hospital Jikei University School of Medicine Aoto 6-41-2, Katsushika-ku Tokyo 125 Japan

Takayuki Ozawa Department of Biomedical Chemistry Faculty of Medicine University of Nagoya 65 Tsuruma-cho, Showa-ku Nagoya 466 Japan

Vincenzo Panagia Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre 351 Tache Avenue Winnipeg, MB R2H 2A6 Canada

Muthu Periasamy Molecular Cardiology Laboratory Division of Cardiology University of Cincinnati College of Medicine 231 Bethesa Avenue, P.O. Box 670542 Cincinnati, OH 45267 USA

Burkert Pieske Universitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg Germany

Philip A. Poole-Wilson Department of Cardiac Medicine National Heart and Lung Institute Dovehouse Street London SW3 6L Y United Kingdom

Miguel Quinones Division of Cardiology Baylor College of Medicine 6550 Fannin, MS SM677 Houston, TX 77030 USA

Hanumanth K. Reddy

List of contributors xxvii

Department of Internal Medicine and Dalton Cardiovascular Research Center University of Missouri One Hospital Drive Columbia, MO 65212 USA

Hans Reinecke U niversitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg Germany

Robert Roberts Division of Cardiology Baylor College of Medicine 6550 Fannin, MS SM677 Houston, TX 77030 USA

xxviii List of contributors

Stephen Schaffer University of South Alabama School of Medicine Department of Pharmacology MSB 3130 Mobile, AL 36688-0002 USA

Jutta Schaper Max-Planck-Institute Department of Experimental Cardiology Benekestrasse 2 0-61231 Bad Nauheim Germany

James Scheuer Division of Cardiology Montefiore Medical Center Albert Einstein College of Medicine 111 East 210th Street Bronx, NY 10467 USA

Michael D. Schneider Molecular Cardiology Unit One Baylor Plaza, Room 506C Baylor College of Medicine Houston, TX 77030 USA

Christine E. Seidman Departments of Genetics and Cardiology Harvard Medical School 200 Longwood A venue Boston, MA 02115 USA

J. G. Seidman Departments of Genetics and Cardiology Harvard Medical School 200 Longwood A venue Boston, MA 02115 USA

Rajat Sethi National Research Council (NRC) Institute for Biodiagnostics 435 Ellice A venue Winnipeg, MB R3B 1Y6 Canada

Junaid Shabbeer Molecular Cardiology Laboratory Division of Cardiology University of Cincinnati College of Medicine 231 Bethesda Avenue, P.O. Bo 670542 Cincinnati, OH 45267 USA

Hari S. Sharma Department of Pharmacology Cardiovascular Research Institute COEUR Faculty of Medicine and Health Sciences Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands

Ichiro Shiojima Internal Medicine III University of Tokyo Tokyo 113 Japan

Andreas Sigel Department of Anesthesiology Yale University School of Medicine 333 Cedar Street P.O. Box 3333 New Haven, CT 06510 USA

Rohit K. Sin gal Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre 351 Tache Avenue Winnipeg, MB R2H 2A6 Canada

List of contributors xxix

xxx List of contributors

Gitte Stawski Department of Medicine B, 2142 Rigshospitalet University of Copenhagen 9 Blegdamsvej DK-2100 Copenhagen 0 Denmark

Roland Studer Universitat Freiburg Medizinische Klinik III Hugstetter Strasse 55 79106 Freiburg Germany

Satoru Sugiyama Department of Biomedical Chemistry Faculty of Medicine University of Nagoya 65 Tsuruma-cho, Showa-ku Nagoya 466 Japan

Drew Sukovich Dupont Merck Pharmaceutical P.O. Box 80400 Wilmington, DE 19880-0400 USA

Bernard Swynghedauw U 127-INSERM Hopital Lariboisiere 41 Bd de la Chapelle 75010 Paris France

Nobuakira Takeda Department of Internal Medicine Aoto Hospital Jikei University School of Medicine Aoto 6-41-2, Katsushika-ku Tokyo 125 Japan

Masashi Tanaka Department of Biomedical Chemistry Faculty of Medicine University of Nagoya 65 Tsuruma-cho, Showa-ku Nagoya 466 Japan

Akira Tanamura Department of Internal Medicine Aoto Hospital Jikei University School of Medicine Aoto 6-41-2, Katsushika-ku Tokyo 125 Japan

Ludwig H. Theirfelder Departments of Genetics and Cardiology Harvard Medical School 200 Longwood A venue Boston, MA 02115 USA

Suresh C. Tyagi

List of contributors xxxi

Department of Internal Medicine, Biochemistry and Dalton Cardiovascular Research Center

University of Missouri One Hospital Drive Columbia, MO 65212 USA

Han A.A. van Heugten Department of Biochemistry Cardiovascular Research Institute COEUR Faculty of Medicine and health Sciences Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands

xxxii List of contributors

Pieter D. Verdouw Thoraxcentre Cardiovascular Research Institute COEUR Faculty of Medicine and Health Sciences Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam The Netherlands

Richard A. Walsh Molecular Cardiology Laboratory Division of Cardiology University of Cincinnati College of Medicine 231 Bethesda Avenue, P.O. Box 670542 Cincinnati, OH 45267 USA

Ruoxiang Wang Department of Clinical Biochemistry University of Toronto 100 College Street Toronto, ON M5G lL5 Canada

Hugh C. Watkins Departments of Genetics and Cardiology Harvard Medical School 200 Longwood A venue Boston, MA 02115 USA

Klaus Wrogemann Department of Biochemistry & Molecular Biology University of Manitoba 302 Basic Medical Sciences Building 730 William Avenue Winnipeg, MB R3E OW3 Canada

Rui-Ping Xiao Laboratory of Cardiovascular Science Gerontology Research Center 4940 Eastern A venue Baltimore, MD 21224 USA

Tsutomu Yamazaki Internal Medicine III University of Tokyo Tokyo 113 Japan

Y oshio Yazaki Internal Medicine III University of Tokyo Tokyo 113 Japan

Makoto Y oneda Department of Biomedical Chemistry Faculty of Medicine University of Nagoya 65 Tsuruma-cho, Showa-ku Nagoya 466 Japan

Robert Young Grace General Hospital 241 LeMarchant Road St. John's, NF AlE 1 pg Canada

Qun-Tao Yu Division of Cardiology Baylor College of Medicine 6550 Fannin, MS SM677 Houston, TX 77030 USA

Radovan Zak Department of Medicine, MC 5105 University of Chicago 5841 S. Maryland Avenue Chicago, IL 60637 USA

Angel Zarain-Herzberg Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre 351 Tache Avenue Winnipeg, MB R2H 2A6 Canada

List of contributors xxxiii

PREFACE

In recent years the reciprocal relationship between cardiac hypertrophy and the development of heart failure has become increasingly clear. But it was not always so. Many of the signs and symptoms of heart failure were described in ancient Egyptian records but were not attributed to the heart until after Harvey discovered the circulation in 1628. The significance of cardiac hypertrophy was slowly appreciated only after Richard Bright described it in renal disease near the mid-17th century. The reason for this delayed recognition was that the effects of heart failure so often manifested in congested lungs and liver, and swollen abdomen and legs, organs remote from the heart, which was not readily identified as the culprit. Today all this has changed, and it is everywhere accepted that when the heart is challenged with an increased workload over a sufficiently long period, it responds by increasing its muscle mass, a phenomenon known as cardiac hypertrophy.

All life adapts to changes in its environment and the heart is no exception. It responds to pressure overload (hypertension), volume overload (valvular disease), loss of muscle (cardiac infarction), muscle disease (cardiomyopathy), and various hormone and metabolic influences by the compensatory process of hypertrophy. At first this is beneficial, and it enables the heart to satisfy an increased demand. However, when the demand is excessive or continues too long, compensatory mechanisms weaken and deteriorate, eventually ending as heart failure. In addition, there is an activation of the sympathetic nervous system as well as of the renin-angiotensin system, and it is generally held that

xxxvi Preface

these mechanisms are beneficial at initial stages but may playa deleterious role in the genesis of cardiac dysfunction if left unattended. Not only do cardiomyocyte abnormalities become apparent in the failing heart, but a loss of responses to adrenergic stimuli involving postreceptor events (signal transduction) is also a major problem.

The mechanisms of transition from compensatory cardiac hypertrophy to

heart failure are many and complex and, as yet, imperfectly understood. At the organ level there is increased muscle mass and an effort to preserve its energy level and contractile strength, but the indispensable underlying changes are at the molecular level. These changes consist of remodeling of subcellular organelles, including extracellular matrix, sarcolemma, sarcoplas­mic reticulum, mitochondria, and myofibrils. However, the exact signals at the molecular level that result in restructuring of subcellular organelles during the development of cardiac hypertrophy and heart failure remain to be discovered. Further progress in understanding the pathogenesis of hyper­trophy and failure, with consequent improvement in the prevention and treatment of heart failure, requires increased knowledge of the nature and behavior of these fundamental processes.

In an effort to meet the challenge of increasing incidence of heart failure, the International Conference on Heart Failure was held in Winnipeg, Canada on May 20-23, 1994. The purpose of the meeting was to bring together leading basic scientists and clinicians to improve our knowledge of the pathophysiology and treatment of cardiac hypertrophy and heart failure. This resulted in a synthesis of state-of-the-art information of molecular biology, cellular physiology, and structure-function relationships in the cardiovas­cular system in health and disease. We present here some selected papers that describe fundamental mechanisms underlying changes in the cellular machinery during the development of cardiac hypertrophy and heart failure. These chapters have been organized in three sections, (A) Genetic and Mole­cular Events, (B) Cellular and Biochemical Mechanisms, and (C) Signal Transduction Abnormalities. We hope that both students and scientists, as well as clinical and experimental cardiologists, will find this book helpful in understanding and managing the perplexing problems of hypertrophy and failure.

Naranjan S. Dhalla Grant N. Pierce

Vincenzo Panagia Robert E. Beamish

Winnipeg, Canada

ACKNOWLEDGMENTS

Our cordial thanks go to Professor Makoto Nagano for his successful pro­motion of collaboration of the Japanese Working Group on Cardiac Structure and Metabolism with the International Conference on Heart Failure. The efforts of Dr. Nobuakira Takeda in securing financial support from Japan are gratefully acknowledged. The help of Susan Zettler in the preparation of this book is highly appreciated. Special thanks are due to Mr. Jeffrey Smith and Ms. Melissa Welch and their editorial staff at Kluwer Academic Publishers for their patience, interest, and hard work in assembling this volume. We are grateful to the following institutions and corporations for their generous donations in support of the International Conference on Heart Failure, Winnipeg, Canada (May 2()-23, 1994) as well as publication of this book:

A. Institutions

St. Boniface General Hospital Research Foundation Heart & Stroke Foundation of Manitoba Thomas Sill Foundation Health Sciences Centre Research Foundation Medical Research Council of Canada Department of Cardiology, St. Boniface General Hospital Department of Physiology, University of Manitoba Faculty of Medicine, University of Manitoba The Paul H. T. ThorIakson Foundation

xxxviii Acknowledgments

International Society and Federation of Cardiology - Council on Cellular and Molecular Cardiology

Manitoba Health Research Council

B. Pharmaceutical and Other Companies

Principal Donor: Merck Frosst Canada Inc. Major Donor: Searle Canada Inc. Donors: Bristol Myers Squibb Company

Bristol Myers Squibb Canada Burroughs Well come Inc. Ciba-Geigy Canada Ltd.

Supporters:

Contributors:

Pfizer Canada Inc. Zeneca Pharma Inc.

Medtronic of Canada Ltd. Parke-Davis Rhone-Poulenc Rorer Canada Inc. Sandoz Canada Inc. Servier Canada Inc. Warner Lambert Canada Inc.

Beckman Instruments (Canada) Ltd. Eli Lily Canada Inc. Marion Merrd Dow Canada Miles Canada Inc. Fujisawa Canada Inc. Boots Pharmaceutical

C. Contributors from Japan

Japan Heart Foundation Banyu Pharmaceutical Co. Ltd. Bayer Yakuhin Ltd. Calo International Ltd. Chugai Pharmaceutical Co. Ltd. Ciba-Geigy Oapan) Ltd. Daiichi Pharmaceutical Co. Ltd. Dainippon Pharmaceutical Co. Ltd. Fujisawa Pharmaceutical Co. Ltd. Kaken Pharmaceutical Co. Ltd. Kowa Shinyaku Co. Ltd. Kuramoto Memorial Hospital K yowa Hakkou Kogyo Co. Ltd. Nippon Shinyaku Co. Ltd.

Ono Pharmaceutical Co. Ltd. Otsuka Pharmaceutical Co. Ltd. Pfizer Pharmaceuticals Inc. Sankyo Co. Ltd. Shionogi Co. Ltd. Sumitomo Co. Ltd. Takeda Chemical Industries Co. Ltd. Tanabe Seiyaku Co. Ltd. Toray Medical Co. Ltd. Yoshitomi Pharmaceutical Industries Ltd. Zeria Pharmaceutical Co. Ltd.

Acknowledgments xxxix

HEART HYPERTROPHY AND FAILURE