Molecular Cardiology in Clinical Practice

233 Pages·1999·4.062 MB·English

by  Michael R. Sanders M.D. (auth.), Michael Sanders, John B. Kostis (eds.)

MOLECULAR CARDIOLOGY
IN
CLINICAL PRACTICE
BASIC SCIENCE FOR THE CARDIOLOGIST
1. B. Levy, A. Tedgui (eds.): Biology of the Arterial Wall. 1999
ISBN 0-7923-8458-X
2. M.R. Sanders, J.B. Kostis (eds): Molecular Cardiology in Clinical
Practice. 1999. ISBN 0-7923-8602-7
3. B. Swynghedauw (ed.): Molecular Cardiology for the Cardiologist. Second
Edition. 1998. ISBN: 0-7923-8323-0
MOLECULAR CARDIOLOGY
IN
CLINICAL PRACTICE
edited by
Michael R. Sanders
John B. Kostis
Department of Medicine
University of Medicine and Dentistry of New Jersey
Robert Wood Johnson Medical School
KLUWER ACADEMIC PUBLISHERS
Boston 1 Dordrecht 1 London
Distributors for North, Central and South America:
Kluwer Academic Publishers
101 Philip Drive
Assinippi Park
Norwell, Massachusetts 0206 1 USA
Telephone [phone]
Fax [phone]
E-Mail <kluwer @ wkap.com>
Distributors for all other countries:
Kluwer Academic Publishers Group
Distribution Centre
Post Office Box 322
3300 AH Dsrdrecht, THE NETHERLANDS
Telephone [phone]
Fax [phone]
E-Mail Corderdept @ wkap.nl>
46 Electronic Services <http:Nw%vw.wkap,nb
Library of Congress Cataloging-in-PublieationD ata
Molecular cardiology in clinical practiceledited by Michael R. Sanders, John B.
Kostis.
P. Cm. -- (Basic science for the cardiologist : 2)
Includes index.
ISBN 0-7923-8602-7
.
1. Heart--Diseases-Molecular aspects. I. Sanders, Michael, 1943- 11. Kostis,
John B. 111. Series.
[DNLM: 1. Cardiovascular Diseases--physiopathology. 2. Cardiovascular
Diseases--genetics. WG 120 M7 177 19991 RC682.9.M645 1999
6 16.1'207--dc2 1
DNLMJDLC
for Library of Congress 99-37334
CIP
Copyright 0 1999 by Kluwer Academic Publishers.
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.
Printed in the United States of America
TABLE OF CONTENTS
....................................................................
List of Contributors vii
................................................................................
Foreword.. xi
...................................................................................
Preface.. xv
1. Introduction to Molecular Medicine: A Contemporary View of
Heart Failure
.........................................................
Michael R. Sanders, M. D.. 1
2. Molecular Mechanisms of Myocardial Remodeling
.......................................................
Wilson S. Colucci, M. D.. ..29
3. Pathophysiology of Heart Failure in Regurgitant Valvular
Diseases: Relation to Ventricular Dysfunction and Clinical Debility
Jeffrey S. Borer, M. D., Edmund McM. Herrold, M. D., Ph. D., Clare A.
Hoclzreiter, M.D., Sharada L. Truter, Ph.D., John N. Carter, Ph. D.,
......................................................
Steven M. Goldfine, Ph. D.. 43
4. Coronary Atherothrombosis: Pathophysiology and Clinical
Implications
Avi Fisclzer, M.D., David E. Gutstein, M.D., Zahi A. Fayad, Ph.D.,
.................................................
Valentin Fuster, M. D., Ph. D.. ..57
5. Prevention of Atherosclerosis: Endothelial Function, Cholesterol
And Antioxidants
.............................................................
RobertA. Vogel, M.D 77
6. Physiologic and Pathophysiologic Effects of Angiotensin in the
Heart and Vessel Wall
.......................................................
Riclzard E. Pratt, Ph. D.. 107
7. Regulation of Inflammation by FAS Ligand Expression on the
Vascular Endothelium
........................
Kennetlz Walslz, Plz. D. and Masataka Sata, M. D.. .I25
8. Molecular Mechanisms of Platelet Activation and Inhibition
............................................................
A. Koneti Rao, M. D.. 143
9. Molecular Determinants of the T Wave
.......................................................
Miclzael R.. Rosen, M. D .I69
10. Sexual Dimorphism in Cardiovascular Disease
..............................
Stephen Bakir, M.D., Suzanne Oparil, M.D.. 187
..................................................................................
Index.. 219
LIST OF CONTRIBUTORS
Michael R. Sanders, M.D.
Clinical Professor of Medicine
Director of Molecular Medicine
Department of Medicine
University of Medicine and Dentistry of New Jersey
Robert Wood Johnson Medical School
New Brunswick, N.J. 08903
John B. Kostis, M.D.
John G. Detwiler Professor of Cardiology
Professor of Medicine and Pharmacology
Chairman, Department of Medicine
University of Medicine and Dentistry of New Jersey
Robert Wood Johnson Medical School
New Brunswick, N.J. 08903
Wilson S. Colucci, M.D.
Chief, Cardiovascular Medicine
Professor of Medicine and Physiology
Boston University School of Medicine
Boston, Massachusetts 02 1 18
Jeffrey S.Borer, M.D.
Chief, Division of Cardiovascular Pathophysiology
New York Presbyterian Hospital-Weill Cornell University Medical College
Gladys and Roland Harriman Professor of Cardiovascular Medicine
Professor of Cardiovascular Medicine in Radiology and Cardiothoracic Surgery
Weill Medical College of Cornell University
New York, N.Y. 10021
Edmund McM. Herrold, M.D., Ph.D.
Director, Section of Biomechanics and Biophysics
Division of Cardiovascular Pathophysiology
New York Presbyterian Hospital-Weill Cornell University Medical College
Associate Professor of Medicine and Cardiovascular Medicine in Cardiothoracic
Surgery
Weill Medical College of Cornell University
New York, N.Y. 1002 1
Clare A. Hochreiter, M.D.
Director, Section of Clinical Epidemiology and Clinical Trials
Division of Cardiovascular Pathophysiology
New York Presbyterian Hospital-Weill Cornell University Medical College
Associate Professor of Medicine and Cardiovascular Medicine in Cardiothoracic
Surgery
Weill Medical College of Cornell University
New York, N.Y. 10021
Sharada L. Truter, Ph.D.
Division of Cardiovascular Pathophysiology
New York Hospital-Weill Cornell University Medical College
Assistant Professor of Cell Biology in Medicine and Cell Biology and Anatomy
Well Medical College of Cornell University
New Yrok, N.Y. 10021
John N. Carter, Ph.D.
Division of Cardiovascular Pathophysiology
Research Associate in Cardiovascular Surgery
Weill Medical College of Cornell University
Adjunct Assistant Professor of Chemical Engineering
Cornell University
Ithaca, N.Y. 14850
Steven M. Goldfine, Ph.D.
Senior Scientist, Department of Physiology and Biophysics
Health Sciences Center at SUNY Stony Brook
Stony Brook, N.Y. 11 794
Avi Fischer, M.D.
Fellow in Cardiology
Zena and Michael A. Weiner Cardiovascular Institute
Mt. Sinai Medical Center
New York, N.Y. 10029
David E. Gutstein, M.D.
Fellow in Cardiology
Zena and Michael A. Weiner Cardiovascular Institute
Mt. Sinai Medical Center
New York, N.Y. 10029
Zahi A. Fayad, Ph.D.
Director, Cardiovascular Imaging Physics and Research
Assistant Professor
Zena and Michael A. Weiner Cardiovascular Institute and Department of Radiology
Mt. Sinai Medical Center
New York, N.Y. 10029
Valentin Fuster, M.D., Ph.D.
Director, The Zena and Michael A. Weiner Cardiovascular Institute
Richard Gorlin, MD 1 Heart Research Foundation Professor of Cardiology
Dean of Academic Affairs
Mount Sinai Medical Center
New York, N.Y. 10029
Robert A. Vogel, M.D.
Herbert Berger Professor of Medicine
Head, Division of Cardiology
University of Maryland School of Medicine
Baltimore, Maryland 2 120 1
Richard E. Pratt, Ph.D.
Associate Professor of Medicine
Harvard Medical School
Director, Laboratory of Genetic Physiology
Brigham and Women's Hospital
Boston, Massachusetts 02 11 5
Kenneth Walsh, Ph.D.
Associate Professor of Medicine
Tufts University School of Medicine
Boston, Massachusetts 02 11 1
Masataka Sata, M.D.
Senior Physician
Department of Cardiovascular Medicine
Graduate School of Medicine
University of Tokyo
Tokyo, Japan
A.Koneti Rao, M.D.
Professor of Medicine and Thrombosis Research
Director, Thromboembolic Diseases
Temple University School of Medicine
Philadelphia, Pennsylvania 19 140
Michael R. Rosen, M.D.
Gustavus A. Pfeiffer Professor of Pharmacology
Professor of Pediatrics
College of Physicians and Surgeons of Columbia University
New York, N.Y. 10032
Stephen Bakir, M.D.
Associate in Cardiology
Department of Medicine
University of Alabama at Birmingham
Birmingham, Alabama 35294
Suzanne Oparil, M.D.
Director, Vascular Biology and Hypertension of the Division of
Cardiovascular Diseases
Professor of Medicine
University of Alabama at Birmingham
Birmingham, Alabama 35294
It had been several years since I had attended a national meeting of the American
Heart Association Scientific Sessions. While the sessions on clinical cardiology had
the same feel and tone I was long accustomed to, I was struck by the immense
changes which had occurred within the basic scientific sessions. Not only were the
topics foreign to what I had come to expect, but its very essence had undergone a
profound metamorphosis; I found myself inside a molecular biologist's world!
Instead of force-velocity curves or action potentials, the projection screen flourished
Northern blots, PCR gels and supershift assays. Sarcomeres were replaced by
phosphorylation cascades and contractility by apoptosis. Even the style and
demeanor of the speakers had altered, exemplified by the custom of recognizing
laboratory co-workers at the end of each presentation. I supposed that I should not
have been surprised since I had recently noticed the changing format of some
standard cardiology publications to make them look more like basic science
journals.
It was true; cardiology had entered the world of molecular biology on a
large scale. But it was also true that the practicing cardiologists and internists at this
meeting seemed essentially unaware or disinterested in what appeared to me as a
major shift in the emphasis of cardiologic science. There were, in essence, two
parallel populations of attendees at the Scientific Sessions: the clinical and the
scientific. On further reflection, however, it became clear to me that it was not the
lack of awareness or interest that separated the practicing physicians fiom the new
science. Rather, it was the lack of feeling of connectedness, which in turn, I
realized, issued fiom the rapidly expanding field of "molecular cardiology''
distancing itself by the sheer speed of its growth. But deeper, at the core of the
problem, was the change in the very foundation of the basic science that today's
previously trained physicians had been trained in.
While molecular biology is not a new field, it has not until relatively
recently become an essential part of the standard medical school curriculum, an
integral part of physician thinking. It was 1961 when Jacob and Monod proposed
the molecular genetic basis for cellular adaptation, but Claude Bernard's 19"
century model of homeostasis, rather than altered gene expression, has remained the
mainstay of standard medical understanding to most of today's practicing clinicians.
Even "Molecular Medicine" might not be claimed a recent innovation,
recalling Garrod's description of inborn errors of metabolism in 1909, or Pauling's
xii
explanation of the molecular basis of sickle cell disease in 1949. Nevertheless,
the subject "molecular medicine" is not found in a literature search until the 1980's
when a few scant references first appear. It is not until the mid and late 1990's that
this topic becomes significantly represented by a corpulent body of research
publications.
In truth, however, the term "molecular medicine", has taken on a modem
meaning, different from just the biochemical explanation of pathophysiology.
On first consideration, "molecular medicine" might be taken as: the
application of the principles of molecular biology to those issues which have been
traditionally of interest in the practice and science of medicine. However,
experience in post-graduate education of both medical practitioners and medical
scientists has led me to the realization that these are such diverse, although
intersecting worlds, that even their concept of "medicine" is different. Again this
duality! Its background, indeed, inhabits the very history of medicine.
The practice of medicine is the ancient tradition, based on custom and
folklore, in which a sufferer of a subjective feeling of being "unwell" or "sick" (a
symptom) seeks aid in alleviating his distress. A medical practitioner applies some
intervention which he has reason to believe may help. Only recently has medical
science become one of those many different kinds of reasons to believe in the
effectiveness of a medical intervention. Empiricism, that is observation or trial and
error, played only a minor role until the scientific revolution, as seen in the early
contributions of Morgagni, blossoming with eighteenth and nineteenth century
science, as embodied by Jenner, Pasteur, Koch and Virchow.
Medical science, on the other hand, is a recent tradition in which an
individual's symptoms are believed to be caused by a knowable disease process
which has altered normal biologic (biochemical and physiological) mechanisms,
and is therefore understandable in terms of those mechanisms. Medical practice
treats persons who feel unwell, whereas medical science deals with individuals who
are unhealthy. In this sense, a person may feel well but be unhealthy or feel unwell
(sick), yet be entirely healthy. The medical practitioner may seek to have his patient
feel "normal" again - that is, the way he normally feels or feels most of the time.
Medical science seeks to return the patient to "normal" as objectively compared to
other people who are believed or known to be without the disease causing his
symptoms.
Medical science, then, has become a corpus of knowledge about the nature
of the human body and its constituent parts in health and disease, based upon
discoverable laws of nature; and known through proof by observation and
experimentation, imitating the models of the physical sciences. This body of
knowledge in which biological function (physiology) is explained in terms of
observable structure has grown enormously during the past century, as technology
has allowed the size of observable structures to become increasingly smaller: from
organs to tissues to cells and finally to the molecular constituents of those cells.
Medical science has evolved into the science of biochemical physiology, and most
recently has absorbed the principles of molecular biology: hence, "Molecular
Medicine",
Then what are these principles of molecular biology?
The eleventh century monk Gregor Mendle's observations on the
inheritance of traits posed two important questions: (1) How are traits passed on