Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is essential for angiogenesis in health and pathophysiology, and it is currently a major focus for drug targ eting in the development of treatments for diverse human diseases. Recently , we proposed that VEGF could also play a role as a vascular protective fac tor in the adult vasculature and in disease. In this model, vascular protec tion is defined as a VEGF-induced enhancement of endothelial functions that mediate the inhibition of vascular smooth muscle cell proliferation, enhan ced endothelial cell survival, suppression of thrombosis, and anti-inflamma tory effects. A feature of this model is that protective effects of VEGF ar e essentially independent of angiogenesis or endothelial cell proliferation . VEGF-dependent cell survival and VEGF-induced synthesis of nitric oxide a nd prostacyclin are likely to be key mediators of a vascular protective eff ect. Vascular protection should help to improve insight into the underlying mechanisms of cardiovascular actions of VEGF and prove valuable for develo ping novel therapeutic approaches to cardiovascular disease.