title: Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events.
abstract: OBJECTIVE
  The small leucine-rich proteoglycans fibromodulin and lumican are functionally related extracellular matrix proteins involved in the regulation of collagen fiber formation. Fibromodulin-deficient apolipoprotein E-null mice have decreased vascular retention of lipids and reduced development of atherosclerosis suggesting that fibromodulin may influence the disease process. The aim of the present study was to investigate if fibromodulin and lumican are expressed in human carotid plaques and to determine if their expression is associated with the occurrence of preoperative symptoms and with risk for postoperative cardiovascular events.
  
  
  RESULTS
  153 plaques (51% symptomatic) obtained by carotid endarterectomy were included in this study. Plaque content was analyzed by immunohistochemistry and plaque cytokine content by multiplex technology. Fibromodulin and lumican were widely expressed in plaques and fibromodulin expression was significantly higher in symptomatic plaques. Expression of fibromodulin was significantly higher in plaques obtained from patients with diabetes and a high fibromodulin expression was associated with a higher incidence of post-operative cerebrovascular events, whereas no such associations were seen for lumican. Fibromodulin expression also correlated with plaque lipids and several pro-inflammatory cytokines. In addition, fibromodulin expression correlated with low levels of smooth muscle cells and the anti-inflammatory cytokine IL-10.
  
  
  CONCLUSIONS
  These observations support previous experimental findings in mice for a role of fibromodulin in atherosclerosis and provide clinical evidence of the involvement of fibromodulin in the inflammatory processes that characterize atherosclerotic plaque vulnerability. They also suggest that this is of particular importance in diabetes.
authors.affiliation: Department of Experimental Medical Science, Lund University, Biomedicinskt centrum (BMC): C12, 221 84 Lund, Sweden. Electronic address: Annelie.Shami@med.lu.se.
authors.forename: Annelie
authors.initials: A
authors.lastname: Shami
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Clinical Research Center (CRC), Jan Waldenströms gata 35, House 91-12, Skåne University Hospital, 205 02 Malmö, Sweden.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Tengryd
authors.affiliation: Vascular Centre Malmö-Lund, Skåne University Hospital, Ruth Lundskogs Gata 10, 1st Floor, 20502 Malmö, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Asciutto
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Clinical Research Center (CRC), Jan Waldenströms gata 35, House 91-12, Skåne University Hospital, 205 02 Malmö, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Bengtsson
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Clinical Research Center (CRC), Jan Waldenströms gata 35, House 91-12, Skåne University Hospital, 205 02 Malmö, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Department of Experimental Medical Science, Lund University, Biomedicinskt centrum (BMC): C12, 221 84 Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Hultgårdh-Nilsson
authors.affiliation: Department of Cardiology, Clinical Sciences, Lund University, Clinical Research Center (CRC), Jan Waldenströmsg 35, House 91-12, Skåne University Hospital, 205 02 Malmö, Sweden.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000150:complications / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002560:Cerebrovascular Circulation; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D016894:Endarterectomy, Carotid; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D000071235:Fibromodulin; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D007632:Keratan Sulfate / Q000378:metabolism; D008055:Lipids / Q000097:blood; D000071234:Lumican; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000378:metabolism*; D011184:Postoperative Period; D011509:Proteoglycans / Q000378:metabolism*; D012042:Registries; D013548:Sweden
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D016207:Cytokines; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604332:Fmod protein, mouse; C508609:IL10 protein, human; C000604306:LUM protein, human; D008055:Lipids; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D000071235:Fibromodulin; D016753:Interleukin-10; D007632:Keratan Sulfate; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Atherosclerosis; Diabetes; Fibromodulin; Lumican; Vulnerable plaque