Role of vascular endothelial growth factor in regulation of physiological angiogenesis

Evidence accumulating over the last decade has established the fundamental role of vascular endothelial growth factor (VEGF) as a key regulator of nor mal and abnormal angiogenesis. The biological effects of VEGF are mediated by two tyrosine kinase receptors, Flt-1 (VEGFR-1) and KDR (VEGFR-2). The si gnaling and biological properties of these two receptors are strikingly dif ferent. VEGF is essential for early development of the vasculature to the e xtent that inactivation of even a single allele of the VEGF gene results in embryonic lethality. VEGF is also required for female reproductive functio ns and endochondral bone formation. Substantial evidence also implicates VE GF as an angiogenic mediator in tumors and intraocular neovascular syndrome s, and numerous clinical trials are presently testing the hypothesis that i nhibition of VEGF may have therapeutic value.