Morphologic findings of coronary atherosclerotic plaques in diabetics - A postmortem study

Objective - Coronary atherosclerotic plaque composition of diabetic subjects and localization of receptor for advanced glycation end products ( RAGE) and its ligands have not been extensively studied. Method and Results - Hearts from diabetic subjects and age, race, and sex-matched nondiabetic subjects dying suddenly were examined. Coronary arteries were dissected and lesions were evaluated for plaque burden, necrotic core size, and inflammatory infiltrate. The expression of RAGE, the RAGE-binding protein (S100-A12, EN-RAGE), and cell death ( apoptosis) were also determined. Lesions from type II diabetic subjects had larger mean necrotic cores (P = 0.01) and greater total and distal plaque load (P < 0.001) than nondiabetic subjects. Necrotic core size correlated positively with diabetic status, independent of other risk factors. Intimal staining for macrophages, T-cells, and HLA-DR was also significantly greater in diabetic subjects (P = 0.03, P = 0.003, and P < 0.0001), respectively. The association of increased macrophage infiltrate was independent of cholesterol levels and patient age. Expression of RAGE and EN-RAGE was significantly greater in diabetic subjects (P = 0.004) and was associated with apoptotic smooth muscle cells and macrophages. Conclusion - In sudden coronary death, inflammation and necrotic core size play a greater role in the progression of atherosclerosis in diabetic subjects. The expression of RAGE and EN-RAGE may further compromise cell survival and promote plaque destabilization.