Short-term delivery of anti-PlGF antibody delays progression of atherosclerotic plaques to vulnerable lesions

Cardiovasc Res. 2010 Apr 1;86(1):29-36. doi: 10.1093/cvr/cvp380. Epub 2009 Dec 1.

Abstract

Aims: Placental growth factor (PlGF), a homologue of vascular endothelial growth factor, is a pleiotropic cytokine with a pro-inflammatory activity. Previous gene-inactivation studies revealed that the loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an anti-PlGF antibody (alphaPlGF mAb) has not been evaluated yet.

Methods and results: We characterized the potential of short-term delivery of alphaPlGF mAb in inhibiting lesion development in ApoE-deficient mice (apoE(-/-)) and in CD4:TGFbetaRII(DN) x apoE(-/-) mice, a more severe atherosclerosis model. Short-term treatment of alphaPlGF mAb reduces early atherosclerotic plaque size and inflammatory cell infiltration in the lesion.

Conclusion: These pharmacological alphaPlGF mAb results confirm previous genetic evidence that inhibition of PlGF slows down early atherosclerotic lesion development. Furthermore, the phenocopy of genetic and pharmacological loss-of-function strategies underscores that alphaPlGF acts by selectively neutralizing PlGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Diseases* / drug therapy
  • Aortic Diseases* / metabolism
  • Aortic Diseases* / pathology
  • Apolipoproteins E / genetics
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Macrophages / pathology
  • Mice
  • Mice, Mutant Strains
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Placenta Growth Factor
  • Pregnancy Proteins / immunology*
  • Pregnancy Proteins / metabolism*
  • Tunica Intima / metabolism
  • Tunica Intima / pathology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antibodies, Monoclonal
  • Apolipoproteins E
  • Pgf protein, mouse
  • Pregnancy Proteins
  • Vascular Cell Adhesion Molecule-1
  • Placenta Growth Factor