De Meyer, Guido

Emini Veseli, Besa

Martinet, Wim

Perrotta, Paola

Roth, Lynn

Van der Veken, Bieke

Abstract: Atherosclerosis is a complex multifactorial disease that affects large and medium-sized arteries. Rupture of atherosclerotic plaques and subsequent acute cardiovascular complications remain a leading cause of death and morbidity in the Western world. There is a considerable difference in safety profile between a stable and a vulnerable, rupture-prone lesion. The need for plaque-stabilizing therapies is high, and for a long time the lack of a suitable animal model mimicking advanced human atherosclerotic plaques made it very difficult to make progress in this area. Evidence from human plaques indicates that intra-plaque (IP) angiogenesis promotes atherosclerosis and plaque destabilization. Although neovascularization has been widely investigated in cancer, studies on the pharmacological inhibition of this phenomenon in atherosclerosis are scarce, mainly due to the lack of an appropriate animal model. By using ApoE 12/ 12 Fbn1C1039G+/ 12 mice, a novel model of vulnerable plaques, we were able to investigate the effect of pharmacological inhibition of various mechanisms of IP angiogenesis on plaque destabilization and atherogenesis. In the present review, we discuss the following potential pharmacological strategies to inhibit IP angiogenesis: (1) inhibition of vascular endothelial growth factor signalling, (2) inhibition of glycolytic flux, and (3) inhibition of fatty acid oxidation. On the long run, IP neovascularization might be applicable as a therapeutic target to induce plaque stabilization on top of lipid-lowering treatment

Pharmacological strategies to inhibit intra-plaque angiogenesis in atherosclerosis

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