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

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.