The association of coronary artery disease and advanced glycation end-products

Author(s): Craig Basman, Sarah L Fishman, Varinder Singh, Leonid Poretsky

Traditional risk factors are insufficient to explain all cases of Coronary Artery Disease (CAD) in patients with Diabetes Mellitus (DM). Hyperglycemia is the hallmark feature of DM. An increase in the incidence of both micro-and macrovascular complications of diabetes has been observed with increased duration of hyperglycemia. This association persists even after glycemic control has been achieved, suggesting an innate mechanism of “metabolic memory.” Advanced Glycation End products (AGEs) are glycated proteins or lipoproteins that may serve as mediators of metabolic memory due to their increased production in the setting of hyperglycemia and generally slow turnover. Elevated AGE levels can lead to abnormal cross linking of extracellular and intracellular proteins disrupting their normal structure and function. Furthermore, activation of AGE receptors can induce complex signaling pathways leading to increased inflammation, oxidative stress, enhanced calcium deposition, and increased vascular smooth muscle apoptosis, contributing to the development of atherosclerosis. Through these mechanisms, AGEs and their receptors may play important roles in the development and progression of CAD. However, clinical studies regarding the role of AGEs and their receptors in advancing CAD are limited, with contradictory results. Further studies are needed to evaluate the utility of circulating and tissue AGE levels in identifying asymptomatic patients at risk for CAD or to identify patients who may benefit from invasive intervention.