Saul Benedict Freedman, MB, BS, PhD; Jeffrey M. Isner, MD
Note: Jeffrey Isner, MD, died suddenly during the preparation of proofs of the manuscript.
Acknowledgments: The authors thank Rene Tio, MD, James F. Symes, MD, Peter R. Vale, MD, Douglas W. Losordo, MD, and Charles Milliken, BS, MS, who contributed to several of the studies summarized in this paper, and Mrs. Mickey Neely for preparation of the manuscript.
Requests for Single Reprints: Mickey Neely, St. Elizabeth's Medical Center, 736 Cambridge Street, Boston, MA 02135; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Freedman: Department of Cardiology, Concord Repatriation General Hospital, University of Sydney, Hospital Road, Concord, New South Wales 2139, Australia.
A large body of evidence in animal models of ischemia shows that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. Many cytokines have angiogenic activity; those that have been best studied in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown increases in exercise time and reductions in anginal symptoms and have provided objective evidence of improved perfusion and left ventricular function. Larger-scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein and have not yet shown significant improvement in exercise time or angina compared with placebo. Larger-scale placebo-controlled studies of gene transfer are in progress.
Clinical studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors and the utility of adjunctive endothelial progenitor-cell or stem-cell supplementation, to provide safe and effective therapeutic myocardial angiogenesis. Determination of which growth factors or cells are required to optimize therapeutic neovascularization in an individual patient should be a goal of future research.
Freedman SB, Isner JM. Therapeutic Angiogenesis for Coronary Artery Disease. Ann Intern Med. ;136:54–71. doi: 10.7326/0003-4819-136-1-200201010-00011
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Published: Ann Intern Med. 2002;136(1):54-71.
Cardiology, Coronary Heart Disease.
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