Intraplaque neovascularization as a novel therapeutic target in advanced atherosclerosis

Introduction: Atherosclerosis is a lipid-driven inflammatory process with a tremendously high mortality due to acute cardiac events. There is an emerging need for new therapies to stabilize atherosclerotic lesions. Growing evidence suggests that intraplaque (IP) neovascularisation and IP hemorrhages are important contributors to plaque instability.Areas covered: Neovascularization is a complex process that involves different growth factors and inflammatory mediators of which their individual significance in atherosclerosis remains poorly understood. This review discusses different aspects of IP neovascularization in atherosclerosis including the potential treatment opportunities to stabilize advanced plaques. Furthermore, we highlight the development of accurate and feasible in vivo imaging modalities for IP neovascularization to prevent acute events.Expert opinion: Although lack of a valuable animal model of IP neovascularization impeded the investigation of a causal and straightforward link between neovascularization and atherosclerosis, recent evidence shows that vein grafts in ApoE*3 Leiden mice as well as plaques in ApoE(-/-) Fbn1(C1039G+/-) mice are useful models for intraplaque neovessel research. Even though interference with vascular endothelial growth factor (VEGF) signalling has been widely investigated, new therapeutic opportunities have emerged. Cell metabolism, in particular glycolysis and fatty acid oxidation, appears to perform a crucial role in the development of IP neovessels and thereby serves as a promising target.