Collectively, these observations have hinted that atherosclerotic plaques from subjects with DM II are more prone to rupture because of increased inflammatory activity.However, the actual inflammatory activity in plaques has been less well investigated. Using a novel approach to analyze plaque inflammation, determining the total plaque content of chemokines, proinflammatory cytokines, growth factors, © 2014 American Heart Association, Inc. Objective-Diabetes mellitus (DM) type II is increasing rapidly worldwide. Patients with DM II have a greater atherosclerotic burden and higher risk of developing cardiovascular complications. Inflammation has been proposed as the main cause for the high risk of atherosclerotic disease in DM II. In this study, we compared markers of inflammation and fibrous repair in plaques from subjects with and without DM II. Approach and Results-Carotid endarterectomy specimens were obtained from 63 patients with and 131 without DM.Plaque structure, connective tissue proteins, inflammatory cells, and markers were analyzed by immunohistochemistry, ELISA, Mesoscale, and Luminex technology. Carotid plaques from diabetics had lower levels of extracellular matrix proteins, elastin, and collagen, which are critical for plaque stability. Plaques from diabetics had reduced levels of plateletderived growth factor and matrix metalloproteinase-2, both important for tissue repair. No differences were observed in inflammatory markers in plaques from diabetic and nondiabetic patients. Conclusion-This study suggests that atherosclerotic plaques in subjects with DM II are more prone to rupture because of impaired repair responses rather than to increased vascular inflammation. Although this study did not have a mechanistic design, our findings suggest that targeting impaired repair responses in carotid plaques may help to increase our understanding of atherosclerotic plaque development and vulnerability in patients with DM II. MMPs, tissue inhibitors of MMPs (TIMPs), collagen, and elastin, we demonstrate in this study that no significant difference in these inflammatory markers was to be found comparing plaques from subjects with and without DM II. Instead, plaques obtained from subjects with DM II showed markedly reduced levels of stabilizing extracellular matrix (ECM) proteins and growth factors, suggesting that the high risk for a plaque rupture may be attributed to an impaired tissue repair rather than an enhanced inflammatory activity.
Materials and MethodsMaterials and Methods are available in the online-only Supplement.
Results
Clinical Characteristics of the Study CohortSixty-three plaques were obtained from 63 subjects with DM II and 134 plaques were obtained from 131 subjects without DM. Subjects with DM II had higher body mass index and plasma triglycerides, whereas plasma low-density lipoprotein cholesterol levels were lower. Higher numbers of symptomatic plaques were observed in patients with DM II (Table 1). No significant difference (P=0.5) was found comparing patients with DM II (15, 54 [S...