title: Soluble urokinase plasminogen activator receptor is associated with inflammation in the vulnerable human atherosclerotic plaque.
abstract: OBJECTIVE
  Recently, plasma soluble urokinase plasminogen activator receptor (suPAR) has gained interest as a marker of cardiovascular risk. suPAR is released through the cleavage of urokinase plasminogen activator receptor (uPAR), which is found in monocytes, activated T-lymphocytes and endothelial cells, all involved in atherosclerosis. suPAR levels have been well studied in plasma, but no studies have focused on suPAR in human atherosclerotic plaques. The aim of this study was to determine whether suPAR measured in the plaque is associated with symptomatic plaques and plaque inflammation.
  
  
  METHODS
  Plasma and carotid plaques from 162 patients were analyzed. Lipids, collagen, uPAR, and macrophages were measured histologically. Cytokines and suPAR were measured in homogenized plaque extracts using multiplex immunoassay and ELISA, respectively. Plasma levels of suPAR were analysed with ELISA. CD3, CD4, as well as uPAR mRNA expression were assessed with quantitative real-time polymerase chain reaction in plaque homogenates from 123 patients.
  
  
  RESULTS
  Plaque and plasma suPAR levels were higher in symptomatic patients compared with asymptomatic patients. Plaque suPAR levels correlated with plaque content of lipids and macrophages and with proinflammatory chemokines and cytokines monocyte chemoattractant protein 1, tumor necrosis factor α, interleukin 1β, interleukin 6, platelet-derived growth factor AB/BB, monocyte inflammatory protein 1β, regulated on activation normal T-cell expressed and secreted, and s-CD40L. uPAR mRNA and histological staining for uPAR correlated with plaque content of suPAR.
  
  
  CONCLUSIONS
  This study shows that suPAR in human carotid plaques and plasma is associated with the presence of symptoms and that plaque suPAR is associated with the vulnerable inflammatory plaque. These findings strengthen the hypothesis of suPAR as a future marker of vulnerable atherosclerotic plaques.
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Department of Clinical Sciences, Jan Waldenströms gata 35, CRC 91:12, Lund University, and the Clinical Research Unit, Acute Medical Center, Skåne University Hospital, SE-20502 Malmö, Sweden. Andreas.Edsfeldt@med.lu.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Edsfeldt
authors.forename: Mihaela
authors.initials: M
authors.lastname: Nitulescu
authors.forename: Helena
authors.initials: H
authors.lastname: Grufman
authors.forename: Caitriona
authors.initials: C
authors.lastname: Grönberg
authors.forename: Ana
authors.initials: A
authors.lastname: Persson
authors.forename: Marie
authors.initials: M
authors.lastname: Nilsson
authors.forename: Margaretha
authors.initials: M
authors.lastname: Persson
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016893:Carotid Stenosis / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood / Q000235:genetics / Q000276:immunology*; D012307:Risk Factors; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D014657:Vasculitis / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; D015704:CD4 Antigens; D008055:Lipids; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator