VEGF-A(164/165) and PlGF: roles in angiogenesis and arteriogenesis.

Angiogenic cytokines such as vascular endothelial growth factor-A(164/165) (VEGF-A(164/165)) and placenta growth factor (PlGF) are being considered for therapeutic relief of coronary heart disease and other forms of tissue ischemia caused by atherosclerosis. Before proceeding further with clinical testing, it is important to determine what types of new blood vessels these cytokines actually induce and whether they could provide a useful new blood supply to ischemic tissues. In mice, VEGF-A(164/165) induced a transient angiogenic response (mother vessels, glomeruloid bodies, daughter capillaries), and stable arteriovenous malformations, arteriogenesis, and lymphangiogenesis; whereas PlGF only induced the formation of large, stable blood vessels. The large, long-lasting blood vessels induced by VEGF-A(164/165) and PlGF could provide an improved blood supply if positioned proximal to ischemic tissue, but VEGF-A(164/165)'s angiogenic response--which is short lived and accompanied by vascular hyperpermeability, edema, and fibrosis--would seem to offer little therapeutic benefit.