Morphologic Findings of Coronary Atherosclerotic Plaques in Diabetics

Abstract

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 (Pϭ0.01) and greater total and distal plaque load (PϽ0.001) 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 (Pϭ0.03, Pϭ0.003, and PϽ0.0001), 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 (Pϭ0.004) 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.

Coronary Plaque Characteristics in Patients With Diabetes Mellitus Who Presented With Acute Coronary Syndromes

“…OCT is the only intracoronary imaging modality that is capable of visualizing features of plaque vulnerability such as macrophage accumulation and TCFA that has been validated by histology studies 24, 25. Our results demonstrated that patients with DM had a higher prevalence of lipid‐rich plaque and macrophage accumulation at the culprit plaques, indicating a higher level of culprit plaque instability, consistent with previous pathology studies 18, 19…”

“…Patients with DM have greater necrotic cores and increased levels of inflammation characterized as macrophages and T lymphocytes on pathology studies 18, 19. Moreover, poorly controlled DM is associated with a greater lipid burden 18.…”

“…Moreover, poorly controlled DM is associated with a greater lipid burden 18. Intravascular ultrasound studies have shown that patients with DM and ACS have greater plaque burden and necrotic core volume at the culprit lesions compared with patients with ACS but not DM 20, 21.…”

Morphological characteristics of coronary atherosclerosis in diabetes mellitus

“…and compared these with age-and sex-matched nondiabetics dying suddenly from coronary artery atherosclerotic disease (8). The basis for inclusion into the registry of sudden coronary death included either presence of an acute coronary thrombus or severe coronary atherosclerosis (one or more epicardial arteries with 75% or more cross-sectional luminal narrowing) and the absence of noncoronary causes of death at autopsy or prior surgery.…”

“…The interactions between S100 Ca 2+ -modulated proteins and RAGE receptors in the fine regulation of leukocyte trafficking and proliferation has been reviewed (21), but the role of EN-RAGE in atherosclerosis-related inflammation has not been studied. We applied immunohistochemical antibodies against RAGE and EN-RAGE (S100 A12) to coronary plaques of diabetics and nondiabetics (8). Although RAGE was found localized to macrophages, smooth muscle cells and endothelial cells, in both diabetics and nondiabetics, the overall expression of RAGE, as graded semiquantitatively, was significantly greater in diabetics (16.8±6.2 for diabetics and 10.0±6.1 for nondiabetics; P=0.004).…”