VEGF 121

Vascular endothelial growth factor (VEGF or VEGFA), also known as vascular permeability factor (VPF), is a potent mediator of both angiogenesis and vasculogenesis in the fetus and adult (1 3). It is a member of the PDGF family that is characterized by the presence of eight conserved cysteine residues and a cysteineknot structure (4). Humans express alternately spliced isoforms of 121, 145, 165, 183, 189, and 206 amino acids (aa) in length (4). VEGF165 appears to be the most abundant and potent isoform, followed by VEGF121 and VEGF189 (3, 4).

VEGF121 is the only form that lacks a basic heparinbinding region and is freely diffusible (4). Mouse embryos expressing only the corresponding isoform (VEGF120) do not survive to term, and show defects in skeletogenesis (5). Human VEGF121 shares 87% aa sequence identity with corresponding regions of mouse and rat, 93% with feline, equine and bovine, and 91%, 95% and 96% with ovine, canine and porcine VEGF, respectively. VEGF binds the type I transmembrane receptor tyrosine kinases VEGF R1 (also called Flt1) and VEGF R2 (Flk1/ KDR) on endothelial cells (4). Although VEGF affinity is highest for binding to VEGF R1, VEGF R2 appears to be the primary mediator of VEGF angiogenic activity (3, 4). VEGF165 binds the semaphorin receptor, Neuropilin1; VEGF121 binding has also been reported (6). 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 (7, 8). Circulating VEGF levels correlate with disease activity in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus (9). VEGF is induced by hypoxia and cytokines such as IL1, IL6, IL8, oncostatin M and TNFα (3, 4, 10). 

Refererences:

1. Leung, D.W. et al. (1989) Science 246:1306.
2. Keck, P.J. et al. (1989) Science 246:1309.
3. Byrne
8. Thurston, G. (2002) J. Anat. 200:575.
9. Carvalho, J.F. et al. (2007) J. Clin. Immunol. 27:246.
10. Angelo, L.S. and R. Kurzrock (2007) Clin. Cancer Res. 13:2825.