The role of vascular endothelial growth factor in pathological angiogenesis.

Vascular endothelial growth factor (VEGF) is a diffusible endothelial cell-specific mitogen and angiogenic factor that can also increase vascular permeability. By alternative splicing of mRNA, VEGF may exist as one of four different isoforms that have similar biological activities but differ markedly in targeting and bioavailability. The VEGF receptors are specifically expressed in the cell surface of vascular endothelial cells. Recent studies point to VEGF as a major regulator of physiological angiogenesis, such as developmental and reproductive angiogenesis. Furthermore, VEGF appears to be a crucial mediator of blood vessel growth associated with tumors and proliferative retinopathies. The VEGF mRNA is up-regulated in the majority of human tumors and the VEGF protein is increased in the aqueous and vitreous humors of patients with proliferative retinopathies. Anti-VEGF antibodies have the ability to suppress the growth of a variety of tumor cell lines in nude mice and also can inhibit angiogenesis in animal models of intraocular neovascularization. Therefore, strategies aimed at antagonizing VEGF may form the basis for an effective treatment of tumors and retinopathies. Furthermore, VEGF-induced angiogenesis is sufficient to achieve a therapeutic endpoint in models of coronary or limb ischemia.