Growth Factors as a Potential New Treatment for Ischemic Heart Disease

Growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) exert important effects on endothelial cells in vitro and in vivo. This article reviews the effect of these two growth factors on endothelial dysfunction in various animal models of vascular disease: (1) collateral circulation supplying an ischemic territory, (2) balloon injury, and (3) diet-induced experimental atherosclerosis. Endothelial dysfunction may limit the beneficial effects of collateral vessels on tissue perfusion. Administration of VEGF or basic FGF (bFGF) augments collateral development in different models of hindlimb ischemia by enhancing neovascularity and by facilitating the recovery of endothelial function in the collateral circulation. Similarly, studies performed after balloon angioplasty have demonstrated abnormal responses of previously dilated sites to endothelium-dependent agonists. Administration of VEGF or bFGF increases endothelial regrowth and normalizes endothelium-dependent responses after experimental angioplasty. Finally, endothelium-dependent relaxation is impaired in diet-induced experimental atherosclerosis. It was recently demonstrated that hypercholesterolemic rabbits treated with bFGF had significantly better endothelium-dependent responses than those not treated with bFGF. These results show that in vivo administration of the endothelial cell growth factors VEGF and bFGF leads to significant improvement in endothelium-dependent responses and supports the concept of using these growth factors as a new therapeutic strategy for patients with vascular diseases.