Placental Growth Factor (PlGF) and Its Receptor Flt‐1 (VEGFR‐1)

A bstract : Efforts to therapeutically stimulate or inhibit vessel growth have been primarily focused on vascular endothelial growth factor (VEGF) and its receptor VEGFR‐2 (Flk‐1), while little attention has been devoted to the therapeutic potential for angiogenic disorders of placental growth factor (PlGF), a VEGF family member, and its receptor VEGFR‐1 (Flt‐1). However, recent developments and insights could shift that focus to P1GF and Flt‐1. Indeed, PlGF stimulated angiogenesis and collateral growth in ischemic heart and limb with at least a comparable efficiency to VEGF and did not cause side effects associated with VEGF, such as edema or hypotension. An anti‐Flt‐1 antibody suppressed neovascularization in tumors and ischemic retina, and angiogenesis and inflammatory joint destruction in arthritis. The anti‐Flt‐1 antibody also reduced atherosclerotic plaque growth and vulnerability, but the atheroprotective effect was not due to reduced plaque neovascularization. The anti‐inflammatory effects of the anti‐Flt‐1 antibody were attributable to a reduced mobilization of bone marrow‐derived myeloid progenitors into the peripheral blood, a reduced mobilization/differentiation (and impaired infiltration) of Flt‐1‐expressing leukocytes into inflamed tissues, and a defective activation of myeloid cells. Thus, PlGF and Flt‐1 constitute potential candidates for therapeutic modulation of angiogenesis and inflammation.