VASCULAR ENDOTHELIAL GROWTH-FACTOR

An understanding of the mechanisms regulating growth and differentiation of vascular endothelial cells is very important for cardiovascular biology and medicine. Several potential regulators of angiogenesis have been identified, including acidic and basic fibroblast growth factors, epidermal growth factor, platelet-derived endothelial cell growth factor, transforming growth factors alpha and beta and tumor necrosis factor alpha (TNF-alpha). Vascular endothelial growth factor (VEGF) is unique among these agents by virtue of its direct and specific mitogenic effects on endothelial cells combined with the fact that it is a secreted polypeptide. By alternative splicing of mRNA, VEGF may exist in four different isoforms that have similar biologic activities but differ markedly in their secretion pattern. VEGF is emerging as an important regulator of developmental and ovarian angiogenesis. Its action is purely paracrine as it is produced by a variety of cell types, but its receptors are only in endothelial cells. There is no evidence that endothelial cells in vivo produce VEGF. The VEGF mRNA is expressed at high level by a variety of human tumors, suggesting that VEGF may be a tumor angiogenesis factor. This hypothesis is supported by the finding that monoclonal antibodies specific for VEGF are able to suppress tumor growth in vivo. Therefore, VEGF antagonists may be used for the treatment of malignancies and, possibly, other angiogenic diseases. The VEGF protein has therapeutic potential as an inducer of neovascularization in conditions characterized by impaired tissue perfusion like obstructive atherosclerosis.