Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury
Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury
复制标题
TLR 4/Myd 88/NF-κB信号通路对NLRP 3炎症体在冠状动脉微栓塞心肌损伤中的作用
DOI：
10.1159/000490866
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Zhao, Jinmin
中科院分区：
文献类型：
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作者：
Su, Qiang;Li, Lang;Zhao, Jinmin
Background/Aims: Coronary microembolization (CME) is a common complication of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI); Myocardial inflammation, caused by CME, is the main cause of cardiac injury. TLR4/MyD88/NF-kappa B signaling plays an important role in the development of myocardial inflammation, but its effects on CME remain unclear. To assess the cardiac protective effects of TAK-242 (TLR4 specific inhibitor) on CME-induced myocardial injury, and explore the underlying mechanism. Methods: Cardiac function, serum c-troponin I level, microinfarct were examined by cardiac ultrasound, myocardial enzyme assessment, HBFP staining. The levels of TLR4/MyD88/NF-kappa B signaling and NLRP3 inflammasome pathway were detected by ELISA, qRT-PCR and western blot. Results: The results showed inflammatory responses in the myocardium after CME, with increased expression levels of pro-inflammatory factors TNF-alpha, IL-1 beta and IL-18. Meanwhile, TLR4/MyD88/NF-kappa B signaling and the NLRP3 inflammasome were involved in the inflammatory process. TAK-242 administration before CME effectively inhibited the inflammatory response in the rat myocardium after CME and reduced myocardial injury, mainly by inhibiting TLR4/MyD88/NF-kappa B signaling and reducing NLRP3 inflammasome activation. In addition, in vitro assays with neonatal rat cardiomyocytes further confirmed that TLR4/MyD88/NF-kappa B signaling was significantly activated in the inflammatory response of LPS-induced cardiomyocytes, via activation of the NLRP3 inflammasome. Inhibition of TLR4/MyD88/NF-kappa B signaling resulted in increased survival of cardiomyocytes mainly by reducing the release of inflammatory cytokines and decreasing NLRP3 inflammasome activation. Conclusions: TLR4/MyD88/NF-kappa B signaling participates in the inflammatory response of the myocardium after CME, activating the NLRP3 inflammasome, promoting the inflammatory cascade, and aggravating myocardial injury. Blocking TLR4/MyD88/NF-kappa B signaling may help reduce myocardial injury and improve cardiac function after CME. (C) 2018 The Author(s) Published by S. Karger AG, Basel
