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 targeting in the development of treatments for diverse human diseases. Recently, we proposed that VEGF could also play a role as a vascular protective factor in the adult vasculature and in disease. In this model, vascular protection is defined as a VEGF-induced enhancement of endothelial functions that mediate the inhibition of vascular smooth muscle cell proliferation, enhanced endothelial cell survival, suppression of thrombosis, and anti-inflammatory effects. A feature of this model is that protective effects of VEGF are essentially independent of angiogenesis or endothelial cell proliferation. VEGF-dependent cell survival and VEGF-induced synthesis of nitric oxide and prostacyclin are likely to be key mediators of a vascular protective effect. Vascular protection should help to improve insight into the underlying mechanisms of cardiovascular actions of VEGF and prove valuable for developing novel therapeutic approaches to cardiovascular disease.
Zachary
I
I
Department of Medicine, University College London, 5 Univ. St., London WC1E 6JJ, United Kingdom.
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide