TLR4 Expression Is Associated with Left Ventricular Dysfunction in Patients Undergoing Coronary Artery Bypass Surgery.
TLR4 Expression Is Associated with Left Ventricular Dysfunction in Patients Undergoing Coronary Artery Bypass Surgery.
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DOI：
10.1371/journal.pone.0120175
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hochhauser E
中科院分区：
文献类型：
--
作者：
Avlas O;Bragg A;Fuks A;Nicholson JD;Farkash A;Porat E;Aravot D;Levy-Drummer RS;Cohen C;Shainberg A;Arad M;Hochhauser E
Toll样受体4（TLR 4）是在免疫细胞和心脏中表达的先天性免疫受体。心肌缺血后免疫系统的激活导致促炎介质的释放，这可能对心脏功能产生负面影响。本研究的目的是确定是否TLR 4激活外周血单核细胞和心脏组织取自不同程度的心肌功能障碍的冠状动脉疾病引起的，并计划冠状动脉旁路移植术（CABG）手术后12个月前。将接受CABG手术的左心室射血分数≤ 45%的患者（n = 44）（“EF降低”，n = 20）与EF保留>45%的患者（“EF保留"组，n = 24）进行比较。“EF降低”患者表现出单核细胞中TLR 4表达增加（2.78±0.49 vs. 1.76±0.07 rMFI，p = 0.03）。血浆C-反应蛋白、microRNA miR-320 a、脑利钠肽（proBNP）和NADPH氧化酶（NOX 4）水平在“保留EF”和“降低EF”组之间也有显著差异。右心耳中升高的TLR 4基因表达水平与EF（p<0.008）、NOX 4（p<0.008）和miR 320（p<0.04）的表达水平相关。相反，外周血单核细胞TLR 2表达无差异。CABG手术后，所有患者的单核细胞TLR 4表达均下降，在“EF降低”组中达到统计学显著性。TLR 4在取自缺血性心脏病和左心室功能减退患者的外周单核细胞和心脏组织中被激活。冠状动脉血运重建降低TLR 4表达。因此，我们建议TLR 4发挥致病作用，并可能作为缺血性心肌功能障碍的一个额外的标志物。
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.
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影响因子：
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作者：
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