Therapeutic angiogenesis in ischemic heart disease: gene or recombinant vascular growth factor protein therapy?

Abstract

In the last decennium the challenge to research has been to find methods of inducing new vascular growth in ischemic myocardium due to atherosclerotic coronary artery disease, which could not be treated with balloon angioplasty or coronary artery by-pass grafting. Therapeutic angiogenesis with recombinant vascular endothelial growth factor proteins or gene encoding for the proteins is a new potential treatment for cardiovascular disease. The greatest interest and research has been concentrated on basic Fibroblast Growth Factor (FGF1 and FGF2) and Vascular Endothelial Growth Factor A (VEGF-A165 and VEGF-A121). Several small clinical phase I-II safety and efficacy trials with recombinant vascular endothelial growth factor proteins or gene encoding for the proteins have demonstrated that these treatment regimes seem to be safe and the results have been encouraging. However, two large doubleblind randomized placebo-controlled studies with intracoronary infusions of the recombinant proteins FGF2 and VEGF-A165 could not detect any clinical effect. Large scaled phase II studies with gene therapy are in progress. Therapeutic angiogenesis is still a promising new treatment in patients with coronary artery disease. However, more research including large scaled clinical trials is needed before deciding whether the vascular endothelial growth factor therapy either as a gene or a recombinant slow-release protein formulation therapy can be offered to patients with severe coronary artery disease, which cannot be treated with conventional revascularization.