RP105 alleviates myocardial ischemia reperfusion injury via inhibiting TLR4/TRIF signaling pathways

Abstract

The Toll-like receptor 4 (TLR4) signal pathway-induced inflammation is considered to be a crucial link to myocardial ischemia reperfusion injury (MIRI). Our previous study proved that radioprotective 105 kDa protein (RP105), a negative regulator of TLR4, performed a protective role in MIRI by anti-apoptosis approach. However, the mechanism of RP105 cardioprotection of anti-inflammation is still unclear. This study aimed to explore the underlying mechanism of RP105 anti-inflammation effect in MIRI. We established a rat model of MIRI induced by ligation of the left anterior descending coronary artery for 30 min followed by 2 h reperfusion. Animals were pre-infected with Ad-EGFP-RP105, Ad-EGFP or saline at the apex of the heart. All rats were sacrificed to collect blood samples and myocardial tissue and assessed by immunofluorescence, blood biochemical analysis, Evans blue/triphenyltetrazolium chloride (TTC), hematoxylin and eosin (H&E) staining, enzyme-linked immuno sorbent assay (ELISA), western blot analysis, quantitative PCR and electrophoretic mobility shift assay (EMSA). RP105 overexpression with adenovirus vectors reduced serum myocardial enzyme (CK-MB and LDH) activities, decreased myocardial infarct size, mitigated inflammatory factors interferon-β and tumor necrosis factor-α during MIRI. We also found that Ad-RP105 group exerted distinct repression of TLR4/TRIF signal pathway related proteins and mRNAs (TRIF, TBK-1, IRF3 and p-IRF3) with a low transcriptional activity of IRF3. These findings first expounded that RP105 could alleviate the ischemia reperfusion induced inflammatory status in heart via inhibiting TLR4/TRIF signaling pathway and provided a theoretical foundation of RP105 gene in MIRI.

<p>Protective Effect of Pravastatin on Myocardial Ischemia Reperfusion Injury by Regulation of the miR-93/Nrf2/ARE Signal Pathway</p>

“…The other groups established models according to the method of ischemia reperfusion. 20 The anesthetized rats were fixed on the operating table in supine position, and the endotracheal tube was inserted into the rats and connected to the ventilator. The rat's right carotid artery was isolated and inserted into arterial cannula, and connected to Med-Lab system (Nanjing Medease Science and Technology Co., Ltd., Nanjing China).…”

RP105 plays a cardioprotective role in myocardial ischemia reperfusion injury by regulating the Toll‑like receptor 2/4 signaling pathways

“…Md-2 determines the surface expression and signal transmission of Tlr4 (11,16). Transfection of rP105 into cardiocytes significantly decreased the production of pro-inflammatory cytokines to alleviate the heart from Miri by inhibiting both the Tlr4/Myd88 and Tlr4/Tir-domain-containing adapter-inducing interferon-β (TriF) signaling pathways (17,18).…”

Salvianolic acid B protects against myocardial ischaemia-reperfusion injury in rats via inhibiting high mobility group box 1 protein expression through the PI3K/Akt signalling pathway

“…TLR4 (receptor of HMGB1), as an inflammatory factor, has been shown to play a detrimental role in myocardial I/R injury (Wang et al 2016 ; Yang et al 2018 ). Studies have also shown that the activation of TLR4 can aggravate myocardial inflammation and the effective inhibition of TLR4 may be the key to preventing adverse myocardial remodelling (Vilahur and Badimon 2014 ; Lee, Hutchinson and Saint 2016 ).…”