TLR4 Expression Is Associated with Left Ventricular Dysfunction in Patients Undergoing Coronary Artery Bypass Surgery

• Published in: PloS one Vol. 10; no. 6; p. e0120175
• Main Authors: Avlas, Orna, Bragg, Arieh, Fuks, Avi, Nicholson, James D, Farkash, Ariel, Porat, Eyal, Aravot, Dan, Levy-Drummer, Rachel S, Cohen, Cyrille, Shainberg, Asher, Arad, Michael, Hochhauser, Edith
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-06-2015; Public Library of Science (PLoS)
• Subjects: Aged; Auricle; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Brain; Brain natriuretic peptide; C-reactive protein; Cardiovascular disease; Cardiovascular diseases; Coronary artery; Coronary Artery Bypass; Coronary artery disease; Coronary vessels; Cytokines; Female; Gene expression; Genes; Heart attacks; Heart diseases; Heart failure; Heart function; Heart surgery; Humans; Immune system; Inflammation; Ischemia; Laboratories; Life sciences; Male; Medical research; MicroRNAs; MicroRNAs - blood; Middle Aged; miRNA; Monocytes; Monocytes - metabolism; Myocardial ischemia; NAD(P)H oxidase; Neutrophils; NOX4 protein; Patients; Permeability; Plasma levels; Proteins; Ribonucleic acid; RNA; Rodents; Surgery; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - blood; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - blood; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor necrosis factor-TNF; Ventricle; Ventricular Dysfunction, Left - blood; Ventricular Dysfunction, Left - metabolism; Ventricular Dysfunction, Left - surgery; Tel Aviv Israel; Israel
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120175

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.
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.
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.
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.