Recombinant Human VEGF 111 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 normally 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). Additionally, an active ~18 kDa form, VEGF₁₁₁, can be induced in tumor cells by treatment with genotoxic agents and ultraviolet (UV-B) irradiation (5). Like VEGF₁₂₁, VEGF₁₁₁ lacks the basic heparin-binding region encoded by exons 6 and 7, and is freely diffusible (4, 5). VEGF₁₁₁ also lacks major proteolytic cleavage sites encoded by exon 5, giving it additional stability. Human VEGF₁₁₁ shares 87% aa sequence identity with corresponding regions of mouse and rat VEGF, 93% with feline, equine and bovine VEGF, and 91%, 95% and 96% with ovine, canine and porcine VEGF, respectively. All VEGF forms bind the single pass 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). 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 in female during reproductive cycle (3). Pathologically, it is involved in tumor angiogenesis and vascular leakage (6, 7).