Recombinant Human VEGF 165 Protein (293-VE) (2024)

Vascular endothelialgrowth factor (VEGF or VEGF-A), also known as vascular permeability factor(VPF), is a potent mediator of both angiogenesis and vasculogenesis in thefetus and adult (1-3). It is a member of the PDGF family that is characterizedby the presence of eight conserved cysteine residues and a cystine knotstructure (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 potentisoform, followed by VEGF₁₂₁ andVEGF₁₈₉ (3, 4). Isoforms other thanVEGF₁₂₁ contain basic heparin-binding regions and arenot freely diffusible (4). Human VEGF₁₆₅ shares 88% aasequence identity with corresponding regions of mouse and rat, 96% withporcine, 95% with canine, and 93% with feline, equine and bovine VEGF,respectively. VEGF binds the type I transmembrane receptor tyrosine kinases VEGFR1 (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 bethe primary mediator of VEGF angiogenic activity (3, 4).VEGF₁₆₅ binds the semaphorin receptor, Neuropilin-1 andpromotes complex formation with VEGF R2 (5). VEGF is required duringembryogenesis to regulate the proliferation, migration, and survival ofendothelial cells (3, 4). In adults, VEGF functions mainly in wound healing andthe female reproductive cycle (3). Pathologically, it is involved in tumorangiogenesis and vascular leakage (6, 7). Circulating VEGF levels correlatewith disease activity in autoimmune diseases such as rheumatoid arthritis,multiple sclerosis and systemic lupus erythematosus (8). VEGF is induced byhypoxia and cytokines such as IL-1, IL-6, IL-8, oncostatin M and TNF-alpha (3, 4,9).

Due to its role in angiogenesis of blood vessels, tumorand stroma cells use VEGF to stimulate formation of blood vessels and the proliferationand survival of endothelial cells. Specific immunotherapies targeting the VEGFsignaling pathway include the recombinant antibody against VEGF (Bevacizumab),antibodies targeting the main VEGF receptor (VEGFR2), and small moleculeinhibitors against VEGF receptor tyrosine kinases (10). Immune checkpointinhibitors are an important tool in cancer therapies as tumor cells can hijackimmune checkpoint signals to evade detection by immune cells. In addition tostimulating the formation of tumor blood vessels, VEGF has immunosuppressiveeffects by acting on dendritic cells to block their antigen-presenting and Tcell stimulatory functions. Targeting VEGF in combination with other immunecheckpoint ligands or receptors may prove more effective in immunotherapyapproaches to certain cancer types (11). Because of its role in the formationof blood vessels, VEGF is also an important factor in skeletal developmentwhere blood supply and vascularization are crucial. This has made VEGF animportant molecule in regenerative studies for bone repair as sustained releaseof VEGF has been shown to improve the efficiency of bone regeneration(12).