Vasa vasorum in plaque angiogenesis, metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: a malignant transformation

BACKGROUND: Vascularization is an exciting and complex mechanism involving angiogenesis and arteriogenesis. The metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are associated with multiple metabolic toxicities, which result in reactive oxygen species (ROS) due to an elevated tension of oxidative-redox stress and an accelerated atherosclerosis termed atheroscleropathy. RESULTS: This atheroscleropathy is associated with accelerated angiogenesis within the vulnerable, thin-cap fibro-atheroma, prone to rupture resulting in acute coronary syndromes (ACS). The resulting intimopathy with its neovascularization due to angiogenesis of the adventitial vasa vasorum (Vv) is prone to intraplaque hemorrhage (IPH). These IPH are associated with destabilization of the vulnerable plaques resulting in plaque erosion and plaque rupture resulting in ACS. In atheroscleropathy the adventitial Vv invades the plaque in a malignant-like fashion and concurrently is associated with chronic inflammation, as macrophages are being deposited within the shoulder regions of these vulnerable plaques. These angiogenic Vv provide a custom delivery vascular network for multiple detrimental substrates, which further accelerates the growth of these vulnerable plaques and atheroscleropathy. There exists a vascularization paradox in MS and T2DM, in that, angiogenesis within the plaque is induced and arteriogenesis is impaired. CONCLUSION: This review will attempt to provide a database of knowledge regarding the vascularization process (angiogenesis and arteriogenesis) and its mechanisms to better understand the increased cardiovascular risk and the increased morbidity and mortality associated with MS and T2DM.