title: Impaired fibrous repair: a possible contributor to atherosclerotic plaque vulnerability in patients with type II diabetes.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Edsfeldt
authors.affiliation: 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.).
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
authors.affiliation: 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.).
authors.forename: Helena
authors.initials: H
authors.lastname: Grufman
authors.affiliation: 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.).
authors.forename: Mihaela
authors.initials: M
authors.lastname: Nitulescu
authors.affiliation: 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.).
authors.forename: Pontus
authors.initials: P
authors.lastname: Dunér
authors.affiliation: 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.).
authors.forename: Eva
authors.initials: E
authors.lastname: Bengtsson
authors.affiliation: 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.).
authors.forename: Inês G
authors.initials: IG
authors.lastname: Mollet
authors.affiliation: 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.).
authors.forename: Ana
authors.initials: A
authors.lastname: Persson
authors.affiliation: 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.).
authors.forename: Marie
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: 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.).
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.affiliation: 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.).
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: 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.).
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
authors.affiliation: 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.).
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002340:Carotid Artery Diseases / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004198:Disease Susceptibility; D016894:Endarterectomy, Carotid; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D005355:Fibrosis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D025341:Principal Component Analysis; D012306:Risk; D012422:Rupture, Spontaneous; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis
chemical_list: D000959:Antihypertensive Agents; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D010982:Platelet-Derived Growth Factor; D019714:Tissue Inhibitor of Metalloproteinases; D008687:Metformin; D020782:Matrix Metalloproteinases
keywords: atherosclerosis; diabetes mellitus; extracellular matrix; inflammation; stroke