Arteriosclerosis, thrombosis, and vascular biology · 2004
Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study.
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Burke Allen P, Kolodgie Frank D, Zieske Arthur, Fowler David R, Weber Deena K, Varghese P Jacob, Farb Andrew, Virmani Renu
Аннотация
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.
METHODS 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.
CONCLUSIONS: 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.
METHODS 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.
CONCLUSIONS: 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.
Предметные рубрики MeSH
AdultApoptosisCalcinosisCase-Control StudiesCoronary Artery DiseaseCoronary ThrombosisDiabetes MellitusFemaleGlycation End Products, AdvancedHLA-DR AntigensHumansHypercholesterolemiaHypertensionMacrophagesMaleMiddle AgedNecrosisReceptor for Advanced Glycation End ProductsReceptors, ImmunologicRisk FactorsS100 ProteinsS100A12 ProteinSmokingT-LymphocytesVasculitis