on May 13, 2004
Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
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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Submitted on March 25, 2004
Accepted on April 29, 2004
Morphologic Findings of Coronary Atherosclerotic Plaques in Diabetics. A Postmortem Study
Allen P. Burke ;
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.
* To whom correspondence should be addressed. 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.
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.
Key words: diabetes mellitus • sudden death • atherosclerosis • receptor for advanced glycation end products • S100A12
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