Recombinant Feline VEGF Protein, CF

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 cystine knot structure (4). Although only a 163 aa form has been characterized in cats, 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). Isoforms other than VEGF₁₂₁ contain basic heparin-binding regions and are not freely diffusible (4). Feline VEGF₁₆₃ shares 90% aa sequence identity with corresponding regions of mouse and rat, 93% with human, bovine and ovine, 96% with porcine and equine, and 83% with canine 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 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).