Elevated circulating levels of heat shock protein 70 are related to systemic inflammatory reaction through monocyte Toll signal in patients with heart failure after acute myocardial infarction
Elevated circulating levels of heat shock protein 70 are related to systemic inflammatory reaction through monocyte Toll signal in patients with heart failure after acute myocardial infarction
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DOI：
10.1016/j.ejheart.2006.03.004
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发表时间：
2006-12-01
影响因子：
18.2
通讯作者：
Nakamura, Motoyuki
中科院分区：
文献类型：
--
作者：
Satoh, Mamoru;Shimoda, Yudai;Nakamura, Motoyuki
背景资料：热休克蛋白70（HSP 70）可能作为免疫系统的“损伤信号”，是Toll样受体4（TLR 4）的内源性配体，介导炎性细胞因子的合成，目的：探讨AMI后循环HSP 70水平与单核细胞TLR 4活化及心肌损伤的关系。本研究检测了52例AMI患者和20例对照组的循环HSP 70和单核细胞TLR 4水平，并使用HSP 70刺激的单核细胞分析了离体炎症细胞因子的产生。AMI患者发病后第1天循环HSP 70水平高于对照组，并在发病后14天持续升高。AMI患者HSP 70水平与单核细胞TLR 4、血浆IL-6和TNF-α水平呈正相关。发病14天后，AMI合并心力衰竭组（n = 15）的HSP 70水平高于无心力衰竭组。在我们的体外研究中，HSP 70刺激的单核细胞导致剂量依赖性TLR 4表达和炎性细胞因子的释放。结论：AMI后循环中HSP 70水平升高可能参与了TLR 4信号介导的免疫应答，并参与了AMI后心力衰竭的发生发展。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Background: Recent studies have shown that heat shock protein (HSP) 70 may serve as a "damage signal" to the immune system and could be the endogenous ligand for Toll-like receptor (TLR) 4 mediating synthesis of inflammatory cytokines.Aims: To explore the relationship between circulating HSP70 levels and activation of monocyte TLR4 and myocardial damage after AMI.Methods and results: This study examined circulating HSP70 and monocyte TLR4 levels in 52 patients with AMI and 20 controls, and analyzed ex vivo inflammatory cytokine productions using HSP70-stimulated monocytes. Circulating HSP70 levels were higher in AMI patients on day I after onset than in controls and remained elevated in AMI patients 14 days after onset. HSP70 levels were positively correlated with monocyte TLR4, plasma interleukin-6 and tumor necrosis factor-alpha levels in AMI patients. HSP70 levels 14 days after onset were higher in AMI patients with heart failure (n = 15) than in those without heart failure. In our in vitro study, HSP70-stimulated monocytes resulted in dose-dependent TLR4 expression and release of inflammatory cytokines. TLR4 antibody inhibited inflammatory cytokines release.Conclusions: Elevated circulating levels of HSP70 may be involved in TLR4 signal-mediated immune response and the progression of heart failure after AMI. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.