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Amid the criticisms levied at gene therapy researchers recently, the positive (yet preliminary) advances in therapies designed to elicit angiogenesis for the treatment of ischemic vascular disease, such as the current report by Vale and colleagues,1 are a breath of fresh air for cardiovascular specialists and their patients. Although therapeutic angiogenesis is still in its nascent stages (and its benefits unproven), the contrarian tactics employed by this group are reaping dividends. Whereas the standard approach of gene therapists has been to use viral-based vectors to treat otherwise lethal diseases, the scientists attempting to evoke therapeutic angiogenesis in this report chose to treat patients in whom the benefits may be primarily symptomatic, and they used a relatively low-tech, non–viral-based delivery system.The notion that collateral circulation can protect ischemic tissues is not new; it dates back to the observations of early angiographers, who discovered that patients with severe coronary artery disease and preserved ventricular function frequently formed networks of collateral vessels. However, the ability to augment collateral vessel formation awaited the discovery of specific angiogenic factors. Several groups embraced the idea that angiogenic factors, such as vascular endothelial growth factor (VEGF), could be harnessed to improve the perfusion of ischemic tissues. Indeed, early animal studies were promising, demonstrating that recombinant VEGF administered intravenously enhanced collateral formation in ischemic tissues.2 3 Demonstrating that a single injection of VEGF was effective provided a proof-of-principle experiment. However, it was unclear whether this strategy would be translatable to humans given the differences in the pharmacodynamics and pharmacokinetics of these growth factors and the complexity added by the presence of underlying atherosclerosis in human patients. Some investigators chose to modulate the delivery of angiogenic proteins so that their effects were concentrated and sustained, for example, by intrapericardial delivery.4 Others, including the group led …

Therapeutic Myocardial Angiogenesis Via Vascular Endothelial Growth Factor Gene Therapy