title: Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization.
abstract: BACKGROUND
  Although the participation of inflammation in atherogenesis is widely recognized, the identification of the different components has not been clarified. In particular, the role of inflammation in plaque destabilization is not fully understood.
  
  
  RESULTS
  Our main findings were as follows: (1) In a microarray experiment, we identified visfatin, one of the most recently identified adipokines, as a gene that was markedly enhanced in carotid plaques from symptomatic compared with plaques from asymptomatic individuals. This finding was confirmed when carotid plaques from 7 patients with asymptomatic and 14 patients with symptomatic lesions were examined with real-time reverse transcription polymerase chain reaction. (2) Immunohistochemistry showed that visfatin was localized in areas that were rich in lipid-loaded macrophages. (3) The relationship between visfatin and unstable lesions was also found in patients with coronary artery disease, demonstrating a strong visfatin immunostaining in lipid-rich regions within the material obtained at the site of plaque rupture in patients with acute myocardial infarction. (4) Both oxidized low-density lipoprotein and tumor necrosis factor-alpha increased visfatin expression in THP-1 monocytes, with a particularly enhancing effect when these stimuli were combined. (5) Visfatin increased matrix metalloproteinase-9 activity in THP-1 monocytes and tumor necrosis factor-alpha and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked.
  
  
  CONCLUSIONS
  Our findings suggest that visfatin should be regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet Medical Center and University of Oslo, N-0027 Oslo, Norway.
authors.forename: Tuva B
authors.initials: TB
authors.lastname: Dahl
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Mona
authors.initials: M
authors.lastname: Skjelland
authors.forename: Erik
authors.initials: E
authors.lastname: Øie
authors.forename: Arve
authors.initials: A
authors.lastname: Dahl
authors.forename: Annika
authors.initials: A
authors.lastname: Michelsen
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
authors.forename: Siv H
authors.initials: SH
authors.lastname: Tunheim
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Bjørn
authors.initials: B
authors.lastname: Bendz
authors.forename: Serena
authors.initials: S
authors.lastname: Tonstad
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Kirsten
authors.initials: K
authors.lastname: Krohg-Sørensen
authors.forename: David
authors.initials: D
authors.lastname: Russell
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000276:immunology; D050197:Atherosclerosis / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000378:metabolism*; D002460:Cell Line; D003324:Coronary Artery Disease / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology*; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D020780:Matrix Metalloproteinase 9