Vascular endothelial growth factor A isoform 165 (VEGF165) (VEGF165)

Vascular endothelial growth factor A isoform 165 (VEGF165) is the most abundant and biologically active isoform of the VEGF-A protein, generated through alternative splicing of the VEGFA gene [7, 12, 16]. It functions as a critical regulator of angiogenesis and vascular permeability by binding to the tyrosine kinase receptors VEGFR-1 and VEGFR-2, as well as the co-receptor Neuropilin-1 [4, 8, 14]. In physiological conditions, VEGF165 is essential for embryonic development, wound healing, and the maintenance of vascular homeostasis [9, 12]. However, its pathological overexpression is a primary driver of tumor neovascularization and neovascular ocular diseases, including wet age-related macular degeneration and diabetic retinopathy [6, 12, 15]. Therapeutic strategies involve neutralizing VEGF165 using monoclonal antibodies like bevacizumab, decoy receptors like aflibercept, or aptamers like pegaptanib to inhibit vessel growth and reduce edema [4, 10]. Despite its clinical efficacy, targeting VEGF165 can lead to systemic safety concerns such as hypertension, proteinuria, and impaired wound healing due to its role in normal vascular maintenance [9, 15, 17].

Other names

VEGF-A165VEGF165aVascular permeability factorVPFVEGF-A isoform 165

Neutralization of VEGF-A isoforms to prevent binding and activation of VEGFR-1 and VEGFR-2, thereby inhibiting downstream pro-angiogenic signaling pathways such as PI3K/Akt and MAPK/ERK [10, 12, 14].