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

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 (αPlGF mAb) has not been evaluated yet. Methods and results: We characterized the potential of short-term delivery of αPlGF mAb in inhibiting lesion development in ApoE-deficient mice (apoE-/-) and in CD4:TGFβRIIDN x apoE-/- mice, a more severe atherosclerosis model. Short-term treatment of αPlGF mAb reduces early atherosclerotic plaque size and inflammatory cell infiltration in the lesion. Conclusion: These pharmacological αPlGF 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 αPlGF acts by selectively neutralizing PlGF. © The Author 2009.