Smooth muscle cell pathophysiology and advanced glycation end products (AGEs)

Abstract

Accelerated atherosclerosis is the leading cause of coronary heart disease and stroke, which could account for high mortality rates in patients with diabetes. Although several hyperglycemia-elicited metabolic and hemodynamic derangements have been implicated in the pathogenesis of cardiovascular disease (CVD) in diabetes, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the phenomenon 'metabolic memory' and 'legacy effect', that is, vascular stresses during the diabetic exposure have persisted after glucose normalization. Further, there is a growing body of evidence that a receptor for AGEs (RAGE) is involved in signal transduction of AGEs in a variety of cells. In this paper, we review the role of the AGE-RAGE system in accelerated atherosclerosis, especially focusing on smooth muscle cell pathophysiology, and also discuss the possibility that the AGE/RAGE axis could be a potential therapeutic target for prevention of CVD in patients with diabetes.