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MicroRNA-126a-5p enhances myocardial ischemia-reperfusion injury through suppressing Hspb8 expression

Authors :
Yanjuan Liu
Qinglan Lv
Meidong Liu
Zhongyi Tong
Xianzhong Xiao
Yuanbin Li
Zhenguo Liu
Bimei Jiang
Pengfei Liang
Source :
Oncotarget
Publication Year :
2017
Publisher :
Impact Journals, LLC, 2017.

Abstract

// Bimei Jiang 1 , Yanjuan Liu 1 , Pengfei Liang 2 , Yuanbin Li 1 , Zhenguo Liu 3 , Zhongyi Tong 1 , Qinglan Lv 1 , Meidong Liu 1 and Xianzhong Xiao 1 1 Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, P. R. China 2 Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, P. R. China 3 Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA Correspondence to: Xianzhong Xiao, email: xiaoxianzhong@csu.edu.cn Keywords: microRNA-126a-5p; myocardium; ischemia-reperfusion injury; Hspb8; H9C2 cells Received: April 19, 2017 Accepted: August 23, 2017 Published: October 07, 2017 ABSTRACT Previously, we found several genes are involved in myocardial ischemia-reperfusion (M-I/R) injury. In this report, we first developed a mouse model of M-I/R injury and demonstrated microRNA-126a-5p was associated with the M-I/R injury by using high-throughput microRNA expression analysis. We further investigated the expression and function of microRNA-126a-5p during mouse M-I/R injury. We observed high expression of microRNA-126a-5p in the M-I/R mice and increased levels of LDH and CK-MB (damage markers) in the serum. H 2 O 2 and hypoxia/reoxygenation (H/R) treatment significantly increased the expression of microRNA-126a-5p in H9C2 cells in concentration- and time-dependent manners. Moreover, microRNA-126a-5p overexpression in H9C2 cells inhibited cell viability but increased LDH release and caspase 3 activity. Cardiac function analysis based on the measurements of hemodynamic parameters showed that microRNA-126a-5p expression ablation in M-I/R injured mice led to the reversal of the symptoms caused by M-I/R injury. Transesophageal echocardiography also revealed that the values of LVIDd and LVIDs were decreased while the values of LVFS% and LVEF% were increased in M-I/R injured mice after treatment with microRNA-126a-5p inhibitor, compared with the M-I/R injured mice treated with the control. Bioinformatic analysis demonstrated that Hspb8, a protective protein in myocardium, was the target of microRNA-126a-5p. Thus, these findings indicated that microRNA-126a-5p was up-regulated in mouse M-I/R model and promoted M-I/R injury in vivo through suppressing the expression of Hspb8, which may shed light on the development of potential therapeutic target for M-I/R injury.

Details

ISSN :
19492553
Volume :
8
Database :
OpenAIRE
Journal :
Oncotarget
Accession number :
edsair.doi.dedup.....52c6b57e3e6d24d6f302f149eedf5d20