Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)

Current enthusiasm for the therapeutic application of angiogenesis to a wid e range of disease processes derives in large part from studies of one of t he most potent and biologically important growth factors, vascular permeabi lity factor/vascular endothelial growth factor (VPF/VEGF). VPF/VEGF, also k nown as VEGF-A, is the foremost member of a large family of growth factors, which includes VEGF-B, VEGF-C, VEGF-D,VEGF-E, and placenta growth factor ( PIGF). VPF/VEGF acts as a key regulator in the angiogenic process by induci ng hyperpermeability, proliferation, and migration of endothelial cells. Mo re recently, VPF/VEGF has become recognized for its important role in promo ting endothelial cell survival. The biological actions of VPF/VEGF are medi ated through two tyrosine kinase receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KD R/Flk-1), selectively expressed on vascular endothelium, together with a re cently discovered receptor, neuropilin. Expression of VPF/VEGF and its rece ptors is regulated primarily by hypoxia, other cytokines, oncogenes, and tu mor suppressor genes. The signaling mechanisms of endothelial cell prolifer ation, migration, and hyperpermeability and the role of the anti-apoptotic AKT pathway in endothelial survival are areas of active research. Angiogenesis mediated through VPF/VEGF is pivotal to the pathological entit ies of wound healing, ischemia, and tumor growth. Methods of detection and quantitation of VPF/VEGF in tissues and body fluids have become increasingl y important as VPF/VEGF gains clinical importance in the diagnosis and trea tment of disease.