Recombinant Rat VEGF 164 Protein

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 adult (1-3). It is a member of the PDGF family that is characterized by a cysteine-knot structure formed by eight conserved cysteine residues (4). Alternately spliced isoforms of 121, 145, 165, 183, 189, and 206 amino acids (aa) have been identified in humans, with 120, 164 and 188 aa isoforms found in rat and mouse (2, 4). Isoforms other than VEGF₁₂₀ and VEGF₁₂₁ contain basic heparin-binding regions and are not freely diffusible (4). Rat VEGF₁₆₄ shares 97% aa sequence identity with corresponding regions of mouse, 88% with human and bovine, 89% with porcine and canine, and 90% with feline and equine VEGF, respectively. VEGF binds the type I transmembrane receptor tyrosine kinases VEGF R1 (also called Flt-1) and VEGF R2 (Flk-1/KDR) on endothelial cells (4). Although affinity is highest for binding to VEGF R1, VEGF R2 appears to be the primary mediator of VEGF angiogenic activity (3, 4). Human VEGF₁₆₅ binds the semaphorin receptor, neuropilin-1 and promotes complex formation with VEGF R2 (5). 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-alpha (3, 4, 9).