Vascular growth factors for coronary angiogenesis.
Coronary artery disease not amendable to conventional revascularization poses a significant medical problem. Advances in the understanding of blood vessel growth have given rise to efforts to develop novel therapeutic approaches for these "no-option" patients. Therapeutic angiogenesis makes use of the administration of angiogenic growth factor protein or gene to promote the development of endogenous collateral vessels in ischemic myocardium. Among the growth factors that play a role in blood vessel growth and development, vascular endothelial growth factors (VEGFs) and fibroblast growth factors have been the most extensively studied. Various methods of delivery have been used to enhance localization and persistence. Preliminary animal experiments have been promising with evidence of capillary formation at the target myocardium after growth factor administration. Initial phase I and II clinical trials have been undertaken. Preliminary information on efficacy is beginning to become available, raising hopes and questions about the future direction and potential success of therapeutic angiogenesis as a clinical approach to the treatment of myocardial ischemia. Although the initial clinical results are encouraging, real efficacy has still to be proven and the potential side-effects of these potent angiogenic growth factors remain a concern. Large-scale, randomized, and placebo-controlled studies will be required to demonstrate the true clinical benefit of this novel therapeutic treatment for ischemic heart disease.