Published online before print May 13, 2004, doi: 10.1161/01.ATV.0000131783.74034.97
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 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
This article has been cited by other articles:
 |
|
 |
|
  K Nasu, E Tsuchikane, O Katoh, H Fujita, J-F Surmely, M Ehara, Y Kinoshita, N Tanaka, T Matsubara, Y Asakura, et al. Plaque characterisation by Virtual Histology intravascular ultrasound analysis in patients with type 2 diabetes Heart, April 1, 2008; 94(4): 429 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Golledge, M. Karan, C. S. Moran, J. Muller, P. Clancy, A. E. Dear, and P. E. Norman Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte-matrix interactions Eur. Heart J., March 1, 2008; 29(5): 665 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Heinonen, P. Leppanen, I. Kholova, H. Lumivuori, S.-K. Hakkinen, F. Bosch, M. Laakso, and S. Yla-Herttuala Increased Atherosclerotic Lesion Calcification in a Novel Mouse Model Combining Insulin Resistance, Hyperglycemia, and Hypercholesterolemia Circ. Res., November 9, 2007; 101(10): 1058 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Levy, K. R. Purushothaman, N. S. Levy, M. Purushothaman, M. Strauss, R. Asleh, S. Marsh, O. Cohen, S. K. Moestrup, H. J. Moller, et al. Downregulation of the Hemoglobin Scavenger Receptor in Individuals With Diabetes and the Hp 2-2 Genotype: Implications for the Response to Intraplaque Hemorrhage and Plaque Vulnerability Circ. Res., July 6, 2007; 101(1): 106 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ostling, B. Hedblad, G. Berglund, and I. Goncalves Increased Echolucency of Carotid Plaques in Patients With Type 2 Diabetes Stroke, July 1, 2007; 38(7): 2074 - 2078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-P. Liang, S. Han, T. Senokuchi, and A. R. Tall The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis Circ. Res., June 8, 2007; 100(11): 1546 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hsueh, E. D. Abel, J. L. Breslow, N. Maeda, R. C. Davis, E. A. Fisher, H. Dansky, D. A. McClain, R. McIndoe, M. K. Wassef, et al. Recipes for Creating Animal Models of Diabetic Cardiovascular Disease Circ. Res., May 25, 2007; 100(10): 1415 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pundziute, J. D. Schuijf, J. W. Jukema, E. Boersma, A. J.H.A. Scholte, L. J.M. Kroft, E. E. van der Wall, and J. J. Bax Noninvasive Assessment of Plaque Characteristics With Multislice Computed Tomography Coronary Angiography in Symptomatic Diabetic Patients Diabetes Care, May 1, 2007; 30(5): 1113 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Kanter, F. Johansson, R. C. LeBoeuf, and K. E. Bornfeldt Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques? Circ. Res., March 30, 2007; 100(6): 769 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Levy, J. E. Levy, S. Kalet-Litman, R. Miller-Lotan, N. S. Levy, R. Asaf, J. Guetta, C. Yang, K. R. Purushothaman, V. Fuster, et al. Haptoglobin Genotype Is a Determinant of Iron, Lipid Peroxidation, and Macrophage Accumulation in the Atherosclerotic Plaque Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 134 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Orchard, T. Costacou, A. Kretowski, and R. W. Nesto Type 1 diabetes and coronary artery disease. Diabetes Care, November 1, 2006; 29(11): 2528 - 2538. [Full Text] [PDF]
|
|
|
|
|
|
A. P. Burke, M. Joner, and R. Virmani IVUS-VH: a predictor of plaque morphology? Eur. Heart J., August 2, 2006; 27(16): 1889 - 1890. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jaulmes, S. Thierry, B. Janvier, M. Raymondjean, and V. Marechal Activation of sPLA2-IIA and PGE2 production by high mobility group protein B1 in vascular smooth muscle cells sensitized by IL-1{beta} FASEB J, August 1, 2006; 20(10): 1727 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Marfella, M. D'Amico, K. Esposito, A. Baldi, C. Di Filippo, M. Siniscalchi, F. C. Sasso, M. Portoghese, F. Cirillo, F. Cacciapuoti, et al. The Ubiquitin-Proteasome System and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Rosiglitazone Treatment Diabetes, March 1, 2006; 55(3): 622 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.A. Boisvert, D.M. Rose, A. Boullier, O. Quehenberger, A. Sydlaske, K.A Johnson, L.K. Curtiss, and R. Terkeltaub Leukocyte Transglutaminase 2 Expression Limits Atherosclerotic Lesion Size Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 563 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sato, A. Niessner, S. L. Kopecky, R. L. Frye, J. J. Goronzy, and C. M. Weyand TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque J. Exp. Med., January 23, 2006; 203(1): 239 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Koyama, T. Shoji, H. Yokoyama, K. Motoyama, K. Mori, S. Fukumoto, M. Emoto, T. Shoji, H. Tamei, H. Matsuki, et al. Plasma Level of Endogenous Secretory RAGE Is Associated With Components of the Metabolic Syndrome and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2587 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Toutouzas, V. Markou, M. Drakopoulou, I. Mitropoulos, E. Tsiamis, M. Vavuranakis, S. Vaina, and C. Stefanadis Increased Heat Generation From Atherosclerotic Plaques in Patients With Type 2 Diabetes: An increased local inflammatory activation Diabetes Care, July 1, 2005; 28(7): 1656 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Molnar, S. Yu, N. Mzhavia, C. Pau, I. Chereshnev, and H. M. Dansky Diabetes Induces Endothelial Dysfunction but Does Not Increase Neointimal Formation in High-Fat Diet Fed C57BL/6J Mice Circ. Res., June 10, 2005; 96(11): 1178 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Moreno and V. Fuster New aspects in the pathogenesis of diabetic atherothrombosis J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2293 - 2300. [Abstract] [Full Text] [PDF]
|
|