Vascular endothelial growth factor A and Placental growth factor (VEGF-A and PlGF)

Vascular endothelial growth factor A (VEGF-A) is the principal member of the VEGF family, acting as a secreted dimeric protein that binds and activates two primary receptor tyrosine kinases, VEGFR-1 and VEGFR-2, to drive angiogenesis, vasculogenesis, vascular permeability, and endothelial cell survival. Placental growth factor (PlGF), also a cystine-knot cytokine and homodimer, binds specifically to VEGFR-1 and is critical for pathologic angiogenesis and arteriogenesis in conditions like ischemia, inflammation, and cancer, but less required for developmental vasculature formation. Both factors are targeted by multiple approved drugs (monoclonal antibodies, decoy receptors, small molecules) in cancer, macular degeneration, and other diseases with dysregulated blood vessel growth.

Other names

VEGF (when referring to VEGF-A specifically, sometimes ambiguity remains)PGF (Placenta growth factor, for PlGF)Vascular permeability factor (historical for VEGF-A)PIGF (alternative abbreviation for PlGF in literature)

Most drugs are antagonists or inhibitors: they block the interaction of VEGF-A and/or PlGF with their cognate receptors (VEGFR-1, VEGFR-2), thereby suppressing downstream angiogenic signaling, endothelial cell proliferation, and new vessel formation. Aflibercept acts as a decoy receptor, binding VEGF-A and PlGF with high affinity and sequestering them from signaling. Bevacizumab, ranibizumab, and pegaptanib are monoclonal antibodies or aptamers that neutralize VEGF-A activity. Small molecule kinase inhibitors block VEGFR tyrosine kinase activity.