Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders.
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.
Luttun
Aernout
A
Center for Transgene Technology and Gene Therapy, Flanders Interuniversitary Institute for Biotechnology, Leuven, Belgium.
Tjwa
Marc
M
Carmeliet
Peter
P
D043925:Angiogenesis Inducing Agents / Q000502:physiology*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000502:physiology*
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1