Angiogenesis in atherosclerosis: gathering evidence beyond speculation

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Abstract
The present review summarizes evidence for several functions of neovascularization in plaque growth that sustain perfusion beyond limits of diffusion from the artery lumen and outer adventitial vasa vasorum, deposit proatherogenic plasma molecules, recruit immune cells and progenitors, and promote intraplaque hemorrhage. Recent approvals of antiangiogenesis drugs for clinical use in cancer and macular degeneration improve the feasibility of testing whether such agents inhibit plaque angiogenesis and incidental atherosclerosis. Improvements in large and small animal models of atherosclerosis and knowledge of the molecular regulation of angiogenesis in development and disease have advanced understanding of plaque angiogenesis. Genetic modifications of angiogenesis molecules in mouse strains susceptible to atherosclerosis provide experimental means to identify native molecules that regulate plaque angiogenesis. Studies of plaque angiogenesis are aided by micro-computed tomography techniques that image vasa vasorum anatomy in relation to the atheroma. Greater knowledge of plaque angiogenesis regulation is needed to design treatments that target the most critical regulatory pathways. Evolutions in angiogenesis inhibitor treatments for cancer and other diseases call for a need to understand the distinct cardiovascular profiles of different agents to rationally combine agents for optimal selectivity and efficacy in the intended vascular bed.