Remote Ischemic Postconditioning Protects against Myocardial Ischemia-Reperfusion Injury by Inhibition of the RAGE-HMGB1 Pathway.

Xiangming Wang,Zakaria Iyan,Junhong Wang,Zhijian Yang,Tiantian Tu,Deeraj Mungun,Yan Guo

doi:10.1155/2018/4565630

Abstract

Background The aim of the present study was to observe the effect of RAGE-HMGB1 signal pathway on remote ischemic postconditioning in mice with myocardial ischemia reperfusion injury. Methods Mice model of MIRI was established and randomly divided into three groups: control group, ischemia reperfusion group, and remote ischemic postconditioning group. Infarction size was detected by Evans blue and TTC staining. Cardiac function was detected by echocardiography measurement. The protein levels of RAGE, HMGB1, P-AKT, and ERK1/2 were detected by Western blot 120 min following reperfusion. Results RIPostC could decrease the infarct size and increase LVEF and FS compared with I/R group. Two hours after myocardial ischemia reperfusion, the levels of RAGE and HMGB1 were significantly decreased in RIPostC group compared with those in I/R group. The level of p-AKT was significantly higher in the RIPostC group than in the I/R group. LY294002 significantly attenuated RIPostC-increased levels of Akt phosphorylation. Conclusion RIPostC may inhibit the expression of RAGE and HMGB1 and activate PI3K/Akt signaling pathway to extenuate ischemic reperfusion injury in mice. It could further suppress the oxidative stress, have antiapoptosis effect, and reduce inflammatory reaction, but this effect has certain timeliness.

Highlights

In acute myocardial infarction, timely and effective myocardial reperfusion therapy, such as PCI, CABG, and thrombolytic, is the effective method to limit myocardial infarct area, attenuate clinical symptoms, and improve clinical prognosis
We have found that Remote ischemic postconditioning (RIPostC) limit myocardial infarct size and improve cardiac contractility through the inhibition of RAGE-HMGB1 and activation of Reperfusion Injury Salvage Kinase (RISK) pathways
We demonstrated that (1) RIPostC could provide significant protection against myocardial ischemiareperfusion injury, as evidenced by reduced infarct size and improvement of cardiac function

Summary

Introduction

Timely and effective myocardial reperfusion therapy, such as PCI, CABG, and thrombolytic, is the effective method to limit myocardial infarct area, attenuate clinical symptoms, and improve clinical prognosis. The aim of the present study was to observe the effect of RAGE-HMGB1 signal pathway on remote ischemic postconditioning in mice with myocardial ischemia reperfusion injury. Two hours after myocardial ischemia reperfusion, the levels of RAGE and HMGB1 were significantly decreased in RIPostC group compared with those in I/R group. RIPostC may inhibit the expression of RAGE and HMGB1 and activate PI3K/Akt signaling pathway to extenuate ischemic reperfusion injury in mice. It could further suppress the oxidative stress, have antiapoptosis effect, and reduce inflammatory reaction, but this effect has certain timeliness

Objectives

Methods

Conclusion