title: Brief Report: Proatherogenic Cytokine Microenvironment in the Aortic Adventitia of Patients With Rheumatoid Arthritis.
abstract: Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular disease (CVD) via mechanisms that have not yet been defined. Inflammatory pathways, in particular within the vascular adventitia, are implicated in the pathogenesis of primary CVD but could be amplified in RA at the local tissue level. The aim of this study was to examine the aortic adventitia of coronary artery disease (CAD) patients with or without RA to determine the cytokine profile contained therein.
  
  
  
  Aortic adventitia and internal thoracic artery biopsy specimens obtained from 19 RA patients and 20 non-RA patients undergoing coronary artery bypass graft surgery were examined by immunohistochemistry.
  
  
  
  Interleukin-18 (IL-18), IL-33, and tumor necrosis factor (TNF) were expressed in aortic adventitia biopsy specimens from both groups, and expression of these cytokines was significantly higher in RA patients. In RA patients, IL-33 expression in endothelial cells correlated positively with the number of swollen joints, suggesting a link between the systemic disease state and the local vascular tissue microlesion.
  
  
  
  The presence of the proinflammatory cytokines IL-18, IL-33, and TNF may play a role in the inflammatory process within the adventitia that contributes to plaque formation and destabilization. In theory, the amplified expression of these cytokines may contribute to the known increased occurrence and severity of CAD in patients with RA.
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Ammad
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Hospital for Rheumatic Diseases, Lillehammer, Norway.
authors.forename: Ivana
authors.initials: I
authors.lastname: Hollan
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Curran
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kitson
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Marcello P
authors.initials: MP
authors.lastname: Riggio
authors.affiliation: Hospital for Rheumatic Diseases, Lillehammer, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Mikkelsen
authors.affiliation: University Hospital of North Norway, Tromsø, Norway.
authors.forename: Sven M
authors.initials: SM
authors.lastname: Almdahl
authors.affiliation: Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Carl S
authors.initials: CS
authors.lastname: Goodyear
mesh_terms: D063194:Adventitia / Q000737:chemistry*; D000368:Aged; D001011:Aorta / Q000737:chemistry*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology; D060833:Cellular Microenvironment; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000032:analysis*; D000067596:Interleukin-33 / Q000032:analysis*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: C506536:IL33 protein, human; D020382:Interleukin-18; D000067596:Interleukin-33; D014409:Tumor Necrosis Factor-alpha