Vascular endothelial growth factor (VEGF or VEGF-A), also known as vascular permeability factor (VPF), is a potent mediator of both angiogenesis and vasculogenesis in the fetus and adults (1-3). It is a member of the plateletderived growth factor family that is characterized by a cysteine knot structure formed by eight conserved cysteine residues (4). Mouse embryos expressing only the VEGF120 isoform do not survive to term and show defects in skeletogenesis (5). Mouse VEGF120 shares 98% aa sequence identity with corresponding regions of rat, 89% with canine, feline, equine and porcine, and 87% with human, ovine and bovine VEGF, respectively. VEGF binds the type I transmembrane receptor tyrosine kinases VEGF R1 (also called Flt 1) and VEGF R2 (Flk1/KDR) on endothelial cells (4). VEGF is required during embryogenesis to regulate the proliferation, migration, and survival of endothelial cells (3, 4). In adults, VEGF functions mainly in wound healing and the female reproductive cycle (3). Pathologically, it is involved in tumor angiogenesis and vascular leakage (6, 7). Circulating VEGF levels correlate with disease activity in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus (8).VEGF is induced by hypoxia and cytokines such as IL-1, IL-6, IL-8, oncostatin M and TNF-α (3, 4, 9).
Breier, G. et al. (1992) Development 114:521.
Shima, D.T. et al. (1996) J. Biol. Chem. 271:3877.
Byrne, A.M. et al. (2005) J. Cell. Mol. Med. 9:777.
Robinson, C.J. and S.E. Stringer (2001) J. Cell. Sci.114:853.
Zelzer, E. et al. (2002) Development 129:1893.
Weis, S.M. and D.A. Cheresh (2005) Nature 437:497.
Thurston, G. (2002) J. Anat. 200:575.
Carvalho, J.F. et al. (2007) J. Clin. Immunol. 27:246.
Angelo, L.S. and R. Kurzrock (2007) Clin. Cancer Res.13:2825.
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