Andreas Edsfeldt1, Isabel Gonçalves2, Helena Grufman2, Mihaela Nitulescu2, Pontus Dunér2, Eva Bengtsson2, Inês G Mollet2, Ana Persson2, Marie Nilsson2, Marju Orho-Melander2, Olle Melander2, Harry Björkbacka2, Jan Nilsson2. 1. From the Experimental Cardiovascular Research Unit (A.E., I.G., H.G., M.N., P.D., E.B., A.P., M.N., H.B., J.N.) and Department of Clinical Sciences (I.G.M., M.O.-M., O.M.), Clinical Research Center, Clinical Sciences, Lund University, Malmö, Sweden; and Department of Cardiology-Coronary Diseases, Skåne University Hospital, Malmö, Sweden (A.E., I.G., H.G., A.P., M.N.). Andreas.edsfeldt@med.lu.se. 2. From the Experimental Cardiovascular Research Unit (A.E., I.G., H.G., M.N., P.D., E.B., A.P., M.N., H.B., J.N.) and Department of Clinical Sciences (I.G.M., M.O.-M., O.M.), Clinical Research Center, Clinical Sciences, Lund University, Malmö, Sweden; and Department of Cardiology-Coronary Diseases, Skåne University Hospital, Malmö, Sweden (A.E., I.G., H.G., A.P., M.N.).
Abstract
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 platelet-derived 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.
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 platelet-derived growth factor and matrix metalloproteinase-2, both important for tissue repair. No differences were observed in inflammatory markers in plaques from diabetic and nondiabeticpatients. 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.
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