Vascular endothelial growth factor A (VEGF-165) (VEGF-165)

Vascular endothelial growth factor A (isoform 165), or VEGF-165, is a heparin-binding homodimeric glycoprotein that serves as a master regulator of angiogenesis and vascular permeability (UniProt P15692). It is the most physiologically relevant and frequently overexpressed isoform of the VEGF-A family, acting primarily through the tyrosine kinase receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) on endothelial cells (Ferrara & Adamis, 2016, Nature Reviews Drug Discovery). In oncology, VEGF-165 is secreted by tumor cells to induce the formation of new blood vessels, a process essential for tumor growth beyond a few millimeters and for metastatic spread (NCI Drug Dictionary). In ophthalmology, its excessive production leads to the pathological neovascularization and fluid leakage characteristic of "wet" age-related macular degeneration and diabetic retinopathy (StatPearls, "VEGF Inhibitors"). Therapeutic agents such as bevacizumab, ranibizumab, and the decoy receptor aflibercept target VEGF-165 to inhibit these processes, though pegaptanib specifically targets this 165-amino acid isoform. While effective, inhibition of VEGF-165 can lead to systemic adverse effects including hypertension, proteinuria, and impaired wound healing due to the protein's role in maintaining normal vascular endothelium (FDA, Avastin Prescribing Information).

Other names

VEGF-AVascular permeability factorVPFVEGFA165Vascular endothelial growth factor A165

Neutralization of the circulating growth factor to prevent its binding to VEGFR-1 and VEGFR-2, thereby inhibiting the activation of downstream signaling pathways that drive endothelial cell growth and vascular leakage.