title: Epicardial adipose tissue as a source of nuclear factor-kappaB and c-Jun N-terminal kinase mediated inflammation in patients with coronary artery disease.
abstract: BACKGROUND
  Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated.
  
  
  OBJECTIVE
  The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappaB (NFkappaB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects.
  
  
  METHODS
  Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies.
  
  
  RESULTS
  Western blotting showed epicardial AT had significantly higher NFkappaB, inhibitory-kappaB kinase (IKK)-gamma, IKKbeta, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-alpha. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 +/- 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 +/- 0.57 EU/ml; P<0.05].
  
  
  CONCLUSIONS
  Epicardial AT from patients with CAD shows increased NFkappaB, IKKbeta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFkappaB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.
authors.affiliation: Unit for Diabetes and Metabolism, University of Warwick, Warwick Medical School, Clinical Sciences Research Institute, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, United Kingdom.
authors.forename: A R
authors.initials: AR
authors.lastname: Baker
authors.forename: A L
authors.initials: AL
authors.lastname: Harte
authors.forename: N
authors.initials: N
authors.lastname: Howell
authors.forename: D C
authors.initials: DC
authors.lastname: Pritlove
authors.forename: A M
authors.initials: AM
authors.lastname: Ranasinghe
authors.forename: N F
authors.initials: NF
authors.lastname: da Silva
authors.forename: E M
authors.initials: EM
authors.lastname: Youssef
authors.forename: K
authors.initials: K
authors.lastname: Khunti
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
authors.forename: R S
authors.initials: RS
authors.lastname: Bonser
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: D
authors.initials: D
authors.lastname: Pagano
authors.forename: P G
authors.initials: PG
authors.lastname: McTernan
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D003324:Coronary Artery Disease / Q000150:complications*; D004731:Endotoxins / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis / Q000502:physiology*; D010496:Pericardium / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004731:Endotoxins; D048031:JNK Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C495345:TLR4 protein, human