Vascular endothelial growth factor A, isoform 165 (VEGF165)

VEGF165 is a 46-kDa homodimeric protein consisting of two 165 amino acid polypeptide chains linked by disulfide bonds[6][9]. It is a glycosylated mitogen that specifically acts on endothelial cells and has various effects on vascular development and function[2]. VEGF165 is secreted but approximately 50-70% remains cell- and extracellular matrix-associated due to moderate heparin-surface glycoprotein interactions[6]. VEGF165 is produced by various cells including endothelial cells, macrophages, and T cells[5]. Its expression is induced by hypoxia, inflammatory cytokines, and oncogenes[5]. VEGF165 binds to heparan sulfate and is retained on the cell surface and in the extracellular matrix[5]. VEGF165 is the only VEGF isoform that binds to co-receptors NRP-1 and NRP-2, which enhance VEGFR2 signaling[5]. Although VEGF has higher affinity for VEGFR1, VEGFR2 appears to be the primary mediator of VEGF angiogenic activity[3]. During embryonic development, VEGF165 regulates the proliferation, migration, and survival of endothelial cells[3]. In adults, it functions mainly in wound healing and the female reproductive cycle[3]. Pathologically, VEGF165 is involved in tumor angiogenesis and vascular leakage[3]. It plays a key role in tumor vascularization in many cancers, making it an important target for cancer therapeutics[2][5].

Other names

VEGF-A165Vascular permeability factor (VPF)H-VEGF-165M-VEGF-165

Binds to receptor tyrosine kinases VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR) on endothelial cells; Binds to co-receptors Neuropilin-1 (NRP-1) and Neuropilin-2 (NRP-2); Activates PI3K/AKT, p38 MAPK, FAK and paxillin signaling pathways