Therapeutic angiogenesis: protein-based therapy for coronary artery disease

Therapeutic angiogenesis is a promising treatment for ischaemic heart disease, particularly for patients who are not candidates for current methods of revascularisation. The goal of angiogenic therapy is the relief of symptoms of coronary artery disease and improvement of cardiac function by increasing per-fusion to the ischaemic myocardium. Angiogenic cytokines such as fibroblast growth factor and vascular endothelial growth factor have been studied extensively in preclinical studies. Protein-based therapy with these growth factors has produced functionally significant angiogenesis in several animal models. Enthusiasm following these preclinical results led the way to clinical trials, which so far have shown only modest improvements in myocardial perfusion and clinical outcome. The attenuated angiogenic response to growth factor therapy observed in patients with coronary artery disease may be related to associated conditions such as endothelial dysfunction, regimens of single as opposed to multiple angiogenic agents and inefficiency of current delivery modalities, as illustrated by the disappointing results of the Phase 11 clinical trials using intravascular techniques of administration. The ultimate role angiogenesis will play clinically in the treatment of ischaemic heart disease will be determined by adequately powered, randomised, double-blind, placebo-controlled trials that include multi-agent angiogenic therapy and intramyocardial methods of delivery.