Inhibition of VEGF receptor signaling attenuates intraplaque angiogenesis and plaque destabilization in a mouse model of advanced atherosclerosis

Abstract

Aim: Intraplaque (IP) microvessels have a major causative effect on atherosclerotic plaque development. An increase in microvessel density in ruptured versus nonruptured human plaques suggests that VEGF and other angiogenic factors promote atherosclerosis and potentially destabilize plaques. Because apolipoprotein deficient mice with a heterozygous mutation (C1039G+/-) in the fibrillin-1 gene (ApoE-/-Fbn1C1039G+/-) manifest substantial IP neovascularization, they represent a unique tool to investigate angiogenesis and its role in atherosclerosis. Here, we examined whether administration of axitinib (inhibitor of VEGF receptor-1,-2 and -3) inhibits IP neovascularization and stabilizes atherosclerotic plaques.