Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders

Ann N Y Acad Sci. 2002 Dec;979:80-93. doi: 10.1111/j.1749-6632.2002.tb04870.x.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inducing Agents / physiology*
  • Angiogenesis Inhibitors / therapeutic use*
  • Humans
  • Inflammation / drug therapy
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Physiologic / drug effects*
  • Placenta Growth Factor
  • Pregnancy Proteins / physiology*
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-1 / physiology*

Substances

  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • PGF protein, human
  • Pregnancy Proteins
  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1