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Angiogenesis: Bench to Bedside, Have We Learned Anything?Cardiovascular Division, BIDMC/Harvard Medical School, Boston, Massachusetts 02215, USA Correspondence: Address correspondence to: Roger Laham, Cardiovascular Division, Beth Israel Deaconess Medical Center, One Deaconess Road, Baker 4, Boston, Massachusetts 02215, USA; e-mail:rlaham{at}bidmc.harvard.edu End-stage ischemic cardiomyopathy patients are an ever-increasing group of coronary artery disease patients, often with no options in our current treatment armamentarium. Angiogenesis therapy pre-clinical and phase I clinical trials showed great promise, however, the benefits of single growth factor treatments have not been borne out in the larger phase II randomized trials. The complexity of angiogenesis process and the challenges in creating animal models to replicate and study this process in ischemic adult human myocardium have been major limitations to progress in this field. In addition failure to control for the powerful placebo effect in the clinical trials and inadequate methods of outcomes measures assessment have created difficult to overcome road blocks in establishing the efficacy of angiogenic strategies. Herein we review the challenges of angiogenesis research and development of treatment strategies. We also propose a structured model for further investigations of angiogenic therapies. The adherence to such a regimented approach as proposed here is, in our opinion, the only way to achieve success in angiogenesis approach development to treatment of patients with end-stage cardiac ischemia refractory to other established therapies.
Key Words: Angiogenesis • myogenesis • ischemic heart disease • congestive heart failure • animal models • clinical trials • placebo effect Abbreviations: HUVEC, Human Umbilical Vein Endothelial cells • VEGF, Vascular Endothelial Growth Factor • FGF, Fibroblast Growth Factor • LCX, left circumflex • LAD, left anterior descending • RCA, right coronary artery • PCI, percutaneous coronary interventions • CABG, coronary artery bypass grafting • CHF, congestive heart failure • HGF/SF, hepatocyte growth/scatter factor
Toxicologic Pathology, Vol. 34, No. 1,
3-10 (2006) |
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