title: TLR4 Expression Is Associated with Left Ventricular Dysfunction in Patients Undergoing Coronary Artery Bypass Surgery.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) is an innate immune receptor expressed in immune cells and the heart. Activation of the immune system following myocardial ischemia causes the release of proinflammatory mediators that may negatively influence heart function.
  
  
  OBJECTIVE
  The aim of this study is to determine whether TLR4 is activated in peripheral monocytes and heart tissue taken from patients with varying degrees of myocardial dysfunction caused by coronary artery diseases and scheduled for coronary artery bypass graft (CABG) surgery before 12 months following operation.
  
  
  RESULTS
  Patients (n = 44) undergoing CABG surgery having left ventricular ejection fraction ≤ 45% ('reduced EF', n = 20) were compared to patients with preserved EF >45% ('preserved EF' group, n = 24). 'Reduced EF' patients exhibited increased TLR4 expression in monocytes (2.78±0.49 vs. 1.76±0.07 rMFI, p = 0.03). Plasma levels of C-reactive protein, microRNA miR-320a, brain natriuretic peptide (pro BNP) and NADPH oxidase (NOX4) were also significantly different between the 'preserved EF' and 'reduced EF'groups. Elevated TLR4 gene expression levels in the right auricle correlated with those of EF (p<0.008), NOX4 (p<0.008) and miR320, (p<0.04). In contrast, no differences were observed in peripheral monocyte TLR2 expression. After CABG surgery, monocyte TLR4 expression decreased in all patients, reaching statistical significance in the 'reduced EF' group.
  
  
  CONCLUSIONS
  TLR4 is activated in peripheral monocytes and heart tissue obtained from patients with ischemic heart disease and reduced left ventricular function. Coronary revascularization decreases TLR4 expression. We therefore propose that TLR4 plays a pathogenic role and may serve as an additional marker of ischemic myocardial dysfunction.
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Avlas
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Arieh
authors.initials: A
authors.lastname: Bragg
authors.affiliation: The Cardiac Research Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Fuks
authors.affiliation: The Cardiac Research Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel.
authors.forename: James D
authors.initials: JD
authors.lastname: Nicholson
authors.affiliation: The Cardiac Research Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Farkash
authors.affiliation: The Cardiac Research Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Porat
authors.affiliation: The Cardiac Research Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Aravot
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Levy-Drummer
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Cohen
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Asher
authors.initials: A
authors.lastname: Shainberg
authors.affiliation: Heart Failure Service and Leviev Heart Institute, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Arad
authors.affiliation: The Cardiac Research Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Edith
authors.initials: E
authors.lastname: Hochhauser
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001026:Coronary Artery Bypass; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000097:blood / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000378:metabolism / Q000601:surgery*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4