title: Depot-specific overexpression of proinflammatory, redox, endothelial cell, and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis.
abstract: BACKGROUND
  Pro- and antiinflammatory genes are expressed in epicardial adipose tissue (EAT). Our objectives were to characterize genes in EAT that may contribute specifically to coronary atherogenesis and to measure circulating adipokines matched to their messenger RNAs (mRNAs) in EAT. We hypothesized that severe coronary atherosclerosis (CAD) would preferentially affect gene expression in EAT as compared to substernal fat or subcutaneous thoracic adipose tissue (SAT), as well as circulating levels of adipokines.
  
  
  METHODS
  Fat mRNA was quantified using reverse transcription polymerase chain reaction (RT-PCR), and circulating adipokines were measured by enzyme-linked immunosorbent assays (ELISAs) in patients with severe stable CAD and controls without severe CAD undergoing open heart surgery.
  
  
  RESULTS
  A total of 39 of 70 mRNAs in EAT were significantly increased in CAD. Only 4 and 3 of these mRNAs were increased in substernal fat and SAT, respectively. Of the mRNAs increased in EAT, 17 were either inflammatory adipokines or proteins known to be involved in inflammatory processes, 7 were involved in oxidative stress and or oxygen species regulation, whereas 15 were proteins involved in metabolism and regulation of gene transcription or proteins unique to fat cells. The largest increases, over three-fold, were seen in GPX3, gp91 phox, p47phox, heme oxygenase, and interleukin-8 (IL-8). Tpl2 mRNA was uniquely elevated in all three fat depots from CAD patients, and its expression in SAT, but not in EAT or substernal fat, was directly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) values. Compared to controls, there were no associations between circulating levels of IL-8, lipocalin-2, nerve growth factor (NGF), RANTES, CD-163, GPX-3, monocyte chemotactic protein-1 (MCP-1)/CCL2, leptin, soluble vascular endothelial growth factor receptor-1 (sFLT1), fatty acid binding protein-4 (FABP-4), and plasminogen activator inhibitor-1 (PAI-1) and increases in their gene expression in EAT adjacent to CAD.
  
  
  CONCLUSIONS
  Expression of proinflammatory, redox, endothelial cell, and angiogenic genes in EAT is depot specific and supports the hypothesis that pathophysiologically EAT contributes locally to CAD. CAD links with these fat depots might involve Tpl2 as a primary response indicator.
authors.affiliation: Department of Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, USA. hsacks@hotmail.com
authors.forename: Harold S
authors.initials: HS
authors.lastname: Sacks
authors.forename: John N
authors.initials: JN
authors.lastname: Fain
authors.forename: Paramjeet
authors.initials: P
authors.lastname: Cheema
authors.forename: Suleiman W
authors.initials: SW
authors.lastname: Bahouth
authors.forename: Edward
authors.initials: E
authors.lastname: Garrett
authors.forename: Rodney Y
authors.initials: RY
authors.lastname: Wolf
authors.forename: David
authors.initials: D
authors.lastname: Wolford
authors.forename: Joseph
authors.initials: J
authors.lastname: Samaha
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010084:Oxidation-Reduction; D010496:Pericardium / Q000378:metabolism*; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000235:genetics
chemical_list: D043925:Angiogenesis Inducing Agents; D018836:Inflammation Mediators