title: Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease.
abstract: BACKGROUND
  Inflammatory activity originating from the epicardial adipose tissue (EAT) may have a role in coronary artery disease (CAD) pathogenesis. The relationship between macrophage infiltration, polarization in the EAT, and netrin-1 gene expression was investigated.
  
  
  METHODS
  Macrophage infiltration and polarization were examined by immunohistochemical methods and expression levels of netrin-1, Unc5b, and cytokines related with M1-macrophage subtype (IL-12 and IL-18) were determined by quantitative polymerase chain reaction in subcutaneous and epicardial adipose tissue obtained from patients undergoing coronary artery bypass grafting and non-coronary cardiac surgery.
  
  
  RESULTS
  CAD patients had higher CD68+ (p=0.005) and CD11c+ (p<0.001) macrophage count in EAT when compared to the controls. CD11c+/CD206+ macrophage ratio, which reflects dominancy of M1-macrophage phenotype, was significantly increased in EAT of CAD patients when compared to that of the controls (p=0.008). CAD patients had significantly higher netrin-1, Unc5b, and IL-18 gene expression in the EAT when compared to the control group (p<0.001, p<0.001, and p=0.006 respectively). Increased macrophage infiltration and polarization were associated with higher netrin-1, Unc5b, and IL-12 gene expression in EAT (p<0.05).
  
  
  CONCLUSIONS
  Findings suggest a link between enhanced netrin-1 expression in EAT and macrophage infiltration and polarization in patients with CAD.
authors.affiliation: Department of Histology and Embryology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Kadri Murat
authors.initials: KM
authors.lastname: Gurses
authors.affiliation: Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
authors.forename: Fusun
authors.initials: F
authors.lastname: Ozmen
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Kocyigit
authors.affiliation: Department of Histology and Embryology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Nilgun
authors.initials: N
authors.lastname: Yersal
authors.affiliation: Department of Histology and Embryology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Bilgic
authors.affiliation: Department of Cardiovascular Surgery, Gaziantep University Sahinbey Research and Application Hospital, Gaziantep, Turkey.
authors.forename: Erkan
authors.initials: E
authors.lastname: Kaya
authors.affiliation: Department of Nanotechnology and Nanomedicine, Hacettepe University Graduate School of Science and Engineering, Ankara, Turkey.
authors.forename: Cagla Zubeyde
authors.initials: CZ
authors.lastname: Kopru
authors.affiliation: Department of Cardiovascular Surgery, Medicana International Ankara, Turkey.
authors.forename: Tolga
authors.initials: T
authors.lastname: Soyal
authors.affiliation: Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Suat
authors.initials: S
authors.lastname: Doganci
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Lale
authors.initials: L
authors.lastname: Tokgozoglu
authors.affiliation: Department of Histology and Embryology, Hacettepe University Faculty of Medicine, Ankara, Turkey. Electronic address: petek@hacettepe.edu.tr.
authors.forename: Petek
authors.initials: P
authors.lastname: Korkusuz
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D000368:Aged; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D005260:Female; D015870:Gene Expression; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics*; D000075386:Netrin Receptors; D000075388:Netrin-1; D010496:Pericardium / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D020382:Interleukin-18; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C532445:UNC5B protein, human; D000075388:Netrin-1; D018664:Interleukin-12
keywords: Coronary artery disease; Epicardial adipose tissue; Macrophage polarization; Netrin-1