Recombinant Human VEGF 121 (aa 207-327) 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 the presence of eight conserved cysteine residues and a cysteine-knot 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 heparin-binding 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 Flt-1) and VEGF R2 (Flk-1/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, Neuropilin-1; 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 IL-1, IL-6, IL-8, oncostatin M and TNF-alpha (3, 4, 10).