Abstract

Placental growth factor (PIGF) belongs to a family of vascular endothelial growth factors (VEGF) which includes VEGF itself (also known as VEGF-A) and other homologues like VEGF-B, VEGF-C, VEGF-D, VEGF-E, and PIGF. These growth factors bind to vascular endothelial growth factor receptors (VEGFR) and have been implicated in atherosclerotic plaque instability and coronary neovasculogenensis,^1–4 especially by activating VEGFR-1 found mostly in vascular endothelium. PIGF, originally discovered in placenta, has recently been found in cardiac, pulmonary, musculoskeletal, and thyroid tissues. Endothelial cells produce small amounts of this biomarker, but when stimulated by ischemia or injury, PIGF is produced in copious amounts triggering an angiogenesis switch.² PIGF and VEGFR-1 interaction contributes to angiogenic switch by increasing the crosslinking interaction of VEGFR-1 and VEGFR-2, by amplifying VEGF-A activity on VEGFR-2 and by triggering PIGF-induced signaling on VEGFR-1. The ultimate effects are PIGF-induced endothelial cell enhancement of VEGF angiogenic activity and recruitment of inflammatory cells, hematopoietic stem cells, and vascular stem cells from the bone marrow. Inhibition of PIGF-related VEGFR-1 activation by an anti-VEGFR-1 monoclonal antibody leads to inhibition of inflammation and atherogenic plaque proliferation in animal studies.²