VEGF

VEGF, or vascular endothelial growth factor, is a signal protein family that stimulates the growth of new blood vessels (angiogenesis) and, in some contexts, lymphatic vessels (lymphangiogenesis). It plays a central role in development, wound healing, and pathological neovascularization.

The VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). VEGF-A has several isoforms produced by alternative splicing (for example VEGF-A165). The main receptors are VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4); VEGFR-2 mediates most angiogenic signaling. Co-receptors include neuropilins NRP1 and NRP2. The VEGF ligands have varying affinities for these receptors; VEGF-C and VEGF-D mainly promote lymphangiogenesis via VEGFR-3.

VEGF expression is tightly regulated and upregulated by hypoxia through hypoxia-inducible factors (HIFs). In healthy adults, VEGF is produced by many cell types, including endothelial cells, pericytes, tumor cells, and macrophages.

Dysregulated VEGF signaling contributes to disease. Excess VEGF drives tumor angiogenesis and is a target in cancer therapy; pathological ocular neovascularization underlies wet age-related macular degeneration and diabetic retinopathy, also treated by anti-VEGF agents. Therapies include antibodies or fusion proteins that neutralize VEGF, such as bevacizumab and ranibizumab, and VEGF traps like aflibercept; newer agents target VEGFRs or signaling pathways.

In contrast, therapeutic angiogenesis aims to promote VEGF activity to improve blood flow after ischemic injury. Side effects of anti-VEGF therapy can include hypertension, thrombosis, wound-healing impairment, and ocular inflammation.