ANGIOGENESIS AND DIRECT MYOCARDIAL VASCULARIZATION
CONTEMPORARY CARDIOLOGY
Angiogenesis and Direct Myocardial Revascularization, edited by Roger J.
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CHRISTOPHERP. CANNON,MD SERIES EDITOR
A
NGIOGENESIS ANDD
IRECTM
YOCARDIALR
EVASCULARIZATIONEdited by
ROGER J. LAHAM, MD
Beth Israel Deaconess Medical Center Boston, MA
DONALD S. BAIM, MD
Brigham and Women’s Hospital Boston, MA
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Cover Illustration: Angiogenesis from bench to bedside: tube formation on in vitro matrigel (upper left) A CD31 staining showing increased capillary formation (upper right) A in vivo hind limb ischemia model with increased arterial collaterals (lower left) A cardiac magnetic resonance imaging to detect improvement in perfusion and function (lower right). This translational paradigm with agent discovery rapidly testing in vitro followed by animal models to investigate delivery modalities and efficacy leading to clinical testing with sensitive outcome measures should lead to functionally significant angiogenesis and myogenesis in patients with end-stage ischemic disease and heart failure.
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Library of Congress Cataloging-in-Publication Data
Angiogenesis and direct myocardial revascularization / edited by Roger J. Laham.
p. ; cm. -- (Contemporary cardiology) Includes bibliographical references and index.
ISBN 1-58829-153-7 (alk. paper)
1. Coronary heart disease. 2. Neovascularization.
[DNLM: 1. Neovascularization, Physiologic. 2. Myocardial Revascularization--methods. WG 500 A5842 2005] I. Laham, Roger J. II.
Series: Contemporary cardiology (Totowa, N.J. : Unnumbered).
RC685.C6A595 2005 616.1'23--dc22
2004026636
PREFACE
v
Si facile esset, iam factum sit.
Atherosclerotic disease remains the leading cause of death in the Western Hemisphere, and its prevalence continues to increase as the population ages. Despite progress in surgical and catheter-based revascularization, an ever increasing number of patients are either not candidates for these therapies or remain symptomatic despite prior revascularization and maximal ongoing medical treatment. Thus, it is clear that an alternative treatment strategy such as therapeutic angiogen- esis and myogenesis is needed for these “no-option” patients.
The field of angiogenesis/myogenesis, however, has followed the same development pattern seen with other novel therapeutic interven- tions: early spectacular and “too-good-to-be-true” results leading to unrealistic expectations, followed by sobering complications and disap- pointments, only later maturing to cautious optimism when better under- standing of the biological and logistic obstacles is achieved. We believe that this is such a time for therapeutic angiogenesis/myogenesis, putting behind us the early picture of angiogenesis as “an attempt to influence a process we do not understand, with the agents we do not know how to use and deliver, relying on the end-points we cannot assess.” Unfortu- nately, this led to failure of early studies and a negative view of the field, at a time when we are finally developing a good understanding of the biology and therapeutic targets, have multiple available and well-stud- ied therapeutic strategies, and have developed the necessary imaging to measure outcomes. From here, much work still needs to be done to eventually achieve functionally significant angiogenesis/myogenesis, but clearly we have turned at least the first developmental corner with the identification of novel therapeutic targets and pathways, the investiga- tion of transcriptional factors, master switch molecules, cell-based approaches, chemokines, a better understanding of the effects of aging, endothelial dysfunction, and hypercholesterolemia in response to angiogenic stimuli, as well as a better understanding of delivery prob- lems. Each development has brought us one step closer to our goal of helping patients with end-stage ischemic heart disease, peripheral vas- cular disease, and congestive heart failure.
vi Preface
Angiogenesis and Direct Myocardial Revascularization represents an interdisciplinary effort to balance the basic, preclinical, and clinical aspects in this field. The various sections are each written by pioneers and opinion leaders in angiogenesis/myogenesis. Their chapters reflect the latest developments in this rapidly evolving field, including the in- troduction of cell-based therapy for angiogenesis and myocardial repair.
Wherever this field takes us, we hope that this book will be a useful waypoint, and that we can go forward balancing optimistic enthusiasm with a healthy dose of scientific skepticism, in order to finally realize the promise that such therapies may hold for patients with advanced cardio- vascular disease.
Roger J. Laham, MD
Donald S. Baim, MD
Preface ... v
Contributors ... ix
Color Plates ... xi
1 No-Option Patients: A Growing Problem ... 1
Roger J. Laham and Donald S. Baim 2 Transcriptional Regulation of Angiogenesis ... 19
Peter Oettgen 3 Preclinical Models and Experience to Date ... 37
Aysegul Yegin and Nicolas A. Chronos 4 The Coronary Microcirculation and Angiogenesis ... 65
Pierre Voisine, Joanna J. Wykrzykowska, Munir Boodhwani, David G. Harrison, Roger J. Laham, and Frank W. Sellke 5 Local and Regional Vascular Delivery for Therapeutic Angiogenesis and Myogenesis ... 107
Erik T. Price, Alan C. Yeung, and Mehrdad Rezaee 6 Imaging Angiogenesis: A Guide for Clinical Management and Therapeutic Trials ... 143
Justin D. Pearlman 7 Myocardial Angiogenesis: Protein Growth Factors ... 185
Kwang Soo Cha, Robert S. Schwartz, and Timothy D. Henry 8 Gene Therapy for Angiogenesis in the Treatment of Cardiovascular and Peripheral Arterial Disease ... 215 Pinak B. Shah, Kapildeo Lotun,
and Douglas W. Losordo
CONTENTS
vii
9 Therapeutic Angiogenesis in Peripheral Arterial Disease: Current Approaches
and Future Directions ... 245 Richard E. Waters and Brian H. Annex
10 Bone Marrow Cell Transplantation for Myocardial Regeneration
and Therapeutic Angiogenesis ... 261 Hung-Fat Tse, Pui-Yin Lee, and Chu-Pak Lau 11 Transplantation of Embryonic Stem Cells
for Myocardial Regeneration
and Angiogenesis ... 283 Yong-Fu Xiao, Jiang-Yong Min,
and James P. Morgan 12 Skeletal Myoblast Transplantation
for Cardiac Repair ... 311 Audrey Rosinberg, Jamal S. Rana,
and Roger J. Laham
13 Transmyocardial Laser Revascularization ... 329 Keith A. Horvath
Index ... 349
viii Contents
CONTRIBUTORS
BRIAN H. ANNEX,MD, Division of Cardiology, Department
of Medicine, Duke University School of Medicine, Durham, NC DONALDS. BAIM,MD, Division of Cardiology, Brigham and Women’s
Hospital and Harvard Medical School, Boston, MA
MUNIR BOODHWANI,MD, Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, ON, Canada
KWANG SOO CHA,MD, Dong-A University Hospital, Busan, South Korea, and Minneapolis Heart Institute Foundation, Minneapolis, MN NICHOLAS A. CHRONOS,MD, American Cardiovascular Research
Institute, St. Joseph’s Hospital of Atlanta, Atlanta, GA DAVID G. HARRISON,MD, Division of Cardiology, Department
of Medicine, Emory University School of Medicine, Atlanta, GA TIMOTHY D. HENRY,MD, Minneapolis Heart Institute Foundation,
Minneapolis, MN
KEITH A. HORVATH,MD, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD
ROGER J. LAHAM,MD, Department of Medicine, Angiogenesis Research Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
CHU-PAK LAU,MD, Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
PUI-YIN LEE,MBBS, Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
DOUGLAS W. LOSORDO,MD, Division of Cardiovascular Medicine, St.
Elizabeth’s Medical Center, Boston, MA
KAPILDEO LOTUN,MD, Division of Cardiovascular Medicine, St.
Elizabeth’s Medical Center, Boston, MA
JIANG-YONG MIN,MD, Cardiovascular Division, Department
of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
JAMES P. MORGAN,MD,PhD, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
ix
x Contributors PETER OETTGEN,MD, Division of Cardiology, Department of Medicine,
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
JUSTIN D. PEARLMAN,MD,ME,PhD, Advanced Cardiovascular Imaging Center, Dartmouth Hitchcock Medical Center, Lebanon, NH ERIK T. PRICE,MD, Division of Cardiovascular Medicine, Stanford
University Medical Center, Stanford, CA
JAMAL S. RANA,MD, Divisions of Cardiology and Cardiothoracic Surgery, Angiogenesis Research Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA MEHRDAD REZAEE,MD,PhD, Division of Cardiovascular Medicine,
Stanford University Medical Center, Stanford, CA
AUDREY ROSINBERG,MD, Divisions of Cardiology and Cardiothoracic Surgery, Angiogenesis Research Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA ROBERT S. SCHWARTZ,MD, Minneapolis Heart Institute Foundation,
Minneapolis, MN
FRANK W. SELLKE,MD, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
PINAK B. SHAH,MD, Division of Cardiovascular Medicine, St.
Elizabeth’s Medical Center, Boston, MA
HUNG FAT-TSE,MD, Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
PIERRE VOISINE,MD, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA RICHARD E. WATERS,MD, Division of Cardiology, Department of
Medicine, Duke University School of Medicine, Durham, NC JOANNA J. WYKRZYKOWSKA,MD, Department of Medicine,
Massachusetts General Hospital, Harvard Medical School, Boston, MA
YONG-FU XIAO,MD, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
AYSEGUL YEGIN,MD, American Cardiovascular Research Institute, St.
Joseph’s Hospital of Atlanta, Atlanta, GA
ALAN C. YEUNG,MD, Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA
COLOR PLATES
Color plates 1–6 appear in an insert following p. 116.
Plate 1 Fig. 2 from Chapter 5; for full caption see p. 117.
Plate 2 Fig. 3 from Chapter 5; for full caption see p. 120.
Plate 3 Fig. 5 from Chapter 5; for full caption see p. 128.
Plate 4 Fig. 1 from Chapter 11; for full caption see p. 287.
Plate 5 Fig. 2 from Chapter 11; for full caption see p. 297.
Plate 6 Fig. 3 from Chapter 11; for full caption see p. 299.
xi
