Increased cytokine response after toll-like receptor stimulation in patients with stable coronary artery disease
Increased cytokine response after toll-like receptor stimulation in patients with stable coronary artery disease
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DOI：
10.1016/j.atherosclerosis.2013.09.036
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发表时间：
2013-12-01
期刊：
影响因子：
5.3
通讯作者：
Hoefer, I. E.
中科院分区：
文献类型：
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作者：
Elsenberg, E. H. A. M.;Sels, J. E. M.;Hoefer, I. E.
目的：动脉粥样硬化与血浆细胞因子水平和Toll样受体（TLR）表达增加有关。然而，很少有人知道TLR配体诱导的细胞因子释放作为冠状动脉疾病（CAD）的生物标志物的潜在用途。在这项研究中，我们调查了TLR配体诱导的细胞因子释放是否与动脉粥样硬化疾病的严重程度及其对未来心血管事件的预测价值。在用10 ng/ml脂多糖（LPS，TLR 4配体）和P3 C 500 ng/ml（TLR 2配体）刺激全血2小时后，测量TNF α、IL-8和IL-6的细胞因子水平。在一个亚组中，剂量-反应曲线使用额外的LPS concentration.Results：LPS诱导的全血释放的TNF α和IL-6，但不是IL-8，是显着高于患者相比，健康对照组。在CAD患者中，TLR反应在与传统危险因素和动脉粥样硬化疾病严重程度（病变血管数量和冠状动脉狭窄程度）相关时几乎没有差异。随访期间发生继发性事件的患者显示TLR应答增加的趋势。此外，CRP水平与TLR诱导的TNF α（CRP 2：2364 pg/ml）和IL-6产生（CRP 2：2250 pg/ml）呈正相关。结论：总之，稳定型心绞痛患者TLR诱导的全血细胞因子释放提示存在冠状动脉粥样硬化，但不能反映其严重程度。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Objective: Atherosclerosis is associated with increased levels of plasma cytokines and expression of Toll-like receptors (TLRs). Yet, little is known about the potential use of TLR ligand induced cytokine release as a biomarker of coronary artery disease (CAD). In this study, we investigated whether TLR ligand induced cytokine release is associated with atherosclerotic disease severity and its predictive value for future cardiovascular events.Methods: Blood samples were obtained from 260 patients with stable angina and 15 healthy controls. Cytokine levels of TNF alpha, IL-8 and IL-6 were measured after 2 h of whole blood stimulation with 10 ng/ml lipopolysaccharide (LPS, TLR4 ligand) and P3C 500 ng/ml (TLR2 ligand). In a subgroup, dose-response curves were created using additional LPS concentrations.Results: LPS induced whole blood release of TNF alpha and IL-6, but not IL-8, was significantly higher in patients compared to healthy controls. Among CAD patients, TLR responses did hardly differ when associated with the presence of traditional risk factors and atherosclerotic disease severity (number of diseased vessels and coronary stenosis degree). Patients with secondary events during follow-up showed a trend towards an increased TLR response. Furthermore, positive associations were found between CRP levels and TLR-induced TNF alpha (CRP2: 2364 pg/ml) and IL-6 production (CRP2: 2250 pg/ml).Conclusion: In conclusion, TLR-induced whole blood cytokine release in patients with stable angina indicates the presence of coronary atherosclerosis but does not reflect its severity. (C) 2013 Elsevier Ireland Ltd. All rights reserved.