title: Circulating cytokines reflect the expression of pro-inflammatory cytokines in atherosclerotic plaques.
abstract: OBJECTIVE
  Inflammation is a key factor in the development of plaque rupture and acute cardiovascular events. Although imaging techniques can be used to identify vulnerable atherosclerotic plaques, we are lacking non-invasive methods, such as plasma markers of plaque inflammation that could help to identify presence of vulnerable plaques. The aim of the present study was to investigate whether increased plasma levels of pro-inflammatory cytokines reflects inflammatory activity within atherosclerotic plaques.
  
  
  RESULTS
  Cytokines were measured using Luminex immunoassay in 200 homogenized plaque extracts and plasma, obtained from 197 subjects undergoing carotid surgery. Plasma levels of macrophage inflammatory protein-1β (MIP-1β), tumor necrosis factor- α (TNF-α) and fractalkine correlated significantly, not only with plaque levels of the same cytokines but also with the abundance of several pro-inflammatory and atherogenic cytokines assessed in plaque tissue. High plasma levels (upper tertile) of MIP-1β, TNF-α and fractalkine identified the presence of a plaque with high inflammation (above median of a score based on the plaque content of MIP-1β, TNF-α, interferon-γ (IFN-γ) and fractalkine) with a sensitivity between 65 and 67% and a specificity between 78 and 83%. Furthermore, this study shows that high plasma levels of MIP-1β, TNF-α and fractalkine predict future transient ischemic attacks.
  
  
  CONCLUSIONS
  Our findings show that the plasma levels of MIP-1β, TNF-α and fractalkine reflect the levels of several pro-atherogenic cytokines in plaque tissue and might be possible plasma markers for a vulnerable atherosclerotic disease. We thereby propose that these cytokines can be used as surrogate markers for the identification of patients with high-risk plaques.
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden; Dept. of Cardiology, Skåne University Hospital, Sweden. Electronic address: Andreas.Edsfeldt@med.lu.se.
authors.forename: Andreas
authors.initials: A
authors.lastname: Edsfeldt
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Grufman
authors.affiliation: Vascular Center Malmö, Skåne University Hospital, Malmö, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Asciutto
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Nitulescu
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden; Dept. of Cardiology, Skåne University Hospital, Sweden.
authors.forename: Ana
authors.initials: A
authors.lastname: Persson
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden; Dept. of Cardiology, Skåne University Hospital, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden; Dept. of Cardiology, Skåne University Hospital, Sweden.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D002560:Cerebrovascular Circulation; D054407:Chemokine CCL4 / Q000097:blood; D054428:Chemokine CX3CL1 / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D016894:Endarterectomy, Carotid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013548:Sweden; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054407:Chemokine CCL4; D054428:Chemokine CX3CL1; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Atherosclerosis; Biomarker; Cytokines; Inflammation