VEGFLiganden

VEGFLiganden, commonly referred to as VEGF ligands, are a family of secreted signaling proteins that bind to vascular endothelial growth factor (VEGF) receptors to control blood vessel formation and lymphatic vessel development. The family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). Each ligand interacts with one or more VEGF receptors (VEGFR-1, VEGFR-2, VEGFR-3), often in combination with co-receptors such as neuropilins, which modulate affinity and signaling strength. VEGF-A is the best characterized member and exists in multiple isoforms produced by alternative splicing, notably VEGF-A165, which differ in heparin-binding properties and receptor activation.

Binding of VEGF ligands to their tyrosine kinase receptors promotes receptor dimerization and autophosphorylation, triggering downstream signaling pathways including PI3K/Akt and MAPK/ERK. These pathways stimulate endothelial cell proliferation, migration, survival, and changes in vascular permeability, collectively driving angiogenesis and, for VEGF-C and VEGF-D, lymphangiogenesis.

Expression of VEGF ligands is tightly regulated and induced by tissue hypoxia and other stimuli. In development, VEGF signaling guides vascular patterning; in adults, it participates in wound healing and responses to ischemia. Pathologically, VEGF signaling supports tumor growth and provides a target for anti-angiogenic therapies.

Therapeutic targeting of VEGF ligands or their receptors, such as with monoclonal antibodies, decoy receptors, or tyrosine kinase inhibitors, is used in cancer treatment and retinal diseases. Side effects can include hypertension and impaired wound healing.