The role of inflammation in type 2 diabetes-driven atherosclerosis

Abstract

Cardiovascular disease is the most frequent and costly complication of type 2 diabetes (T2D). Infl ammation is a shared feature of T2D and cardiovascular disease. Vascular and obesity-mediated infl ammation may be key processes responsible for the accelerated development of atherosclerosis in individuals with T2D. Atherosclerosis begins with an insult to the endothelium and progresses through several stages, including the development of endothelial dysfunction, the accumulation of lipids and immune cells in the vessel intima, and phenotypic changes to the vascular cells, all contributing to the formation of vascular lesions. Infl ammation plays a central role in many of these phases. The metabolic imbalances characteristic of T2D, such as insulin resistance, hyperglycemia, and hyperlipidemia, exacerbate vascular dysfunction and infl ammation, accelerating the progression to advanced atherosclerosis. The expression and production of circulating cytokines and adipokines are altered in T2D, contributing to the proinfl ammatory state in blood vessels and adipose tissue. Epigenetic mechanisms are emerging as a missing link in diabetes etiology and may contribute to accelerated atherosclerosis. Two other forms of vascular disease, restenosis and graft vascular disease, share features with atherosclerosis. The presence of T2D similarly worsens these conditions, putting these individuals at risk for major adverse cardiac events. Further study of the infl ammatory mechanisms and epigenetics will improve our understanding of the role of infl ammation in T2D and accelerated cardiovascular disease, and may provide new personalized therapies to treat these conditions.