title: Epicardial adipocyte hypertrophy: Association with M1-polarization and toll-like receptor pathways in coronary artery disease patients.
abstract: OBJECTIVE
  In coronary artery disease (CAD) epicardial adipose tissue (EAT) shows an elevated inflammatory infiltrate. Toll-like receptors (TLRs) are important mediators of adipose tissue inflammation and they are able to recognize endogenous products released by damaged cells. Because adipocyte death may be driven by hypertrophy, our aim was to investigate in CAD and non-CAD patients the association between EAT adipocyte size, macrophage infiltration/polarization and TLR-2 and TLR-4 expression.
  
  
  RESULTS
  EAT biopsies were collected from CAD and non-CAD patients. The adipocyte size was determined by morphometric analysis. Microarray technology was used for gene expression analysis; macrophage phenotype and TLRs expression were analyzed by immunofluorescence and immunohistochemical techniques. Inflammatory mediator levels were determined by immunoassays. EAT adipocytes were larger in CAD than non-CAD patients and do not express perilipin A, a marker of lipid droplet integrity. In CAD, EAT is more infiltrated by CD68-positive cells which are polarized toward an M1 state (CD11c positive) and presents an increased pro-inflammatory profile. Both TLR-2 and TLR-4 expression is higher in EAT from CAD and observed on all the CD68-positive cells.
  
  
  CONCLUSIONS
  Our findings suggested that EAT hypertrophy in CAD promotes adipocyte degeneration and drives local inflammation through increased infiltration of macrophages which are mainly polarized towards an M1 state and express both TLR-2 and TLR-4.
authors: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy. Electronic address: elena.vianello@unimi.it.
authors: E
authors: E
authors: Vianello
authors: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
authors: E
authors: E
authors: Dozio
authors: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
authors: F
authors: F
authors: Arnaboldi
authors: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
authors: M G
authors: MG
authors: Marazzi
authors: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
authors: C
authors: C
authors: Martinelli
authors: Randox Laboratories LTD, R&D, Crumlin-Antrim, Belfast, Northern Ireland, UK.
authors: J
authors: J
authors: Lamont
authors: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
authors: L
authors: L
authors: Tacchini
authors: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
authors: A
authors: A
authors: Sigrüner
authors: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
authors: G
authors: G
authors: Schmitz
authors: Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy; SMEL-1 Clinical Pathology, I.R.C.C.S. Policlinico San Donato, Milan, Italy.
authors: M M
authors: MM
authors: Corsi Romanelli
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010496:Pericardium / Q000473:pathology*; D000070778:Perilipin-1 / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000070778:Perilipin-1; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Coronary artery disease (CAD); Epicardial adipose tissue (EAT); Macrophages infiltration; Toll-like receptors (TLRs)