VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

Despite the enormous progress made in terms of prevention and early intervention, a pressing need remains to develop innovative therapeutic strategies for ischemic cardiovascular disorders, including acute myocardial infarction, chronic cardiac ischemia, peripheral artery disease and stroke. The induction of new blood vessel formation by delivering angiogenic genes to ischemic tissues continues to appear as a promising, alternative strategy to currently available therapies. In aspiring to induce therapeutic angiogenesis, the members of the vascular endothelial growth factor (VEGF) family have long been recognized as major molecular tools. Remarkably, VEGF family members have recently been recognized to also exert multiple, non-angiogenic effects on various cell types, including neurons, skeletal muscle and cardiac cells. Here, we critically review the VEGF-based therapies that have already reached clinical experimentation and highlight the pleiotropic activities of VEGF factors that might create new opportunities for therapeutic application.