Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1266-1271
Published online before print May 13, 2004, doi: 10.1161/01.ATV.0000131783.74034.97
Published online before print May 13, 2004, doi: 10.1161/01.ATV.0000131783.74034.97
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© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Morphologic Findings of Coronary Atherosclerotic Plaques in Diabetics
A Postmortem Study
From the Department of Cardiovascular Pathology (A.P.B., F.D.K., D.K.W., A.F., R.V.), Armed Forces Institute of Pathology, Washington, DC; Louisiana State University Health Science Center (A.Z.), New Orleans, La; the University of Maryland (D.R.F.), Baltimore, Md; and the Department of Cardiology (J.P.V.), George Washington University Medical Center, Washington, DC.
Correspondence to Dr Renu Virmani, Chairperson, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000. E-mail virmani{at}afip.osd.mil
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.
In sudden coronary death, there is a prominent role of plaque-infiltrating macrophages and T cells in the progression of atherosclerosis in diabetic subjects. The expression of RAGE (receptor for advanced glycation end products) and the binding protein (S100 A12, EN-RAGE) may further compromise cell survival and promote plaque destabilization.
Key Words: diabetes mellitus • sudden death • atherosclerosis • receptor for advanced glycation end products • S100A12
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