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Published on: June 15, 2018
MicroRNA-126a-5p enhances myocardial ischemia-reperfusion injury through suppressing Hspb8 expression
Bimei Jiang1, Yanjuan Liu1, Pengfei Liang2
1Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, P. R. China.
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. H2O2 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.
Insights
MicroRNA-126a-5p is elevated in myocardial ischemia-reperfusion (M-I/R) injury, worsening heart damage. Inhibiting this microRNA in mice improved cardiac function by restoring Hspb8 levels, suggesting a new therapeutic target for M-I/R injury.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- MicroRNA Therapeutics
Background:
- Myocardial ischemia-reperfusion (M-I/R) injury is a significant clinical concern with complex molecular mechanisms.
- Previous studies have identified several genes implicated in M-I/R injury, necessitating further investigation into regulatory factors.
Purpose of the Study:
- To investigate the role and expression of microRNA-126a-5p in a mouse model of M-I/R injury.
- To elucidate the functional impact of microRNA-126a-5p on cardiac cells and overall cardiac function during M-I/R injury.
- To identify the molecular targets of microRNA-126a-5p involved in M-I/R pathogenesis.
Main Methods:
- Development of a mouse model for M-I/R injury.
- High-throughput microRNA expression analysis to identify key microRNAs.
- In vitro studies using H9C2 cells subjected to hypoxia/reoxygenation (H/R) and H2O2 treatment.
- Assessment of cell viability, lactate dehydrogenase (LDH), and caspase 3 activity.
- In vivo cardiac function analysis using hemodynamic measurements and transesophageal echocardiography.
- Bioinformatic analysis to predict microRNA targets.
Main Results:
- MicroRNA-126a-5p expression was significantly upregulated in M-I/R mice, correlating with elevated serum LDH and CK-MB levels.
- H/R and H2O2 treatments increased microRNA-126a-5p expression in H9C2 cells in a dose- and time-dependent manner.
- Overexpression of microRNA-126a-5p in H9C2 cells reduced cell viability and increased LDH release and caspase 3 activity.
- Ablation of microRNA-126a-5p in M-I/R mice reversed cardiac dysfunction, improving hemodynamic parameters and echocardiographic indices (LVIDd, LVIDs, LVFS%, LVEF%).
- Bioinformatic analysis identified heat shock protein B8 (Hspb8) as a direct target of microRNA-126a-5p.
Conclusions:
- MicroRNA-126a-5p is upregulated during M-I/R injury and exacerbates cardiac damage.
- MicroRNA-126a-5p promotes M-I/R injury by suppressing the expression of the protective protein Hspb8.
- Targeting microRNA-126a-5p represents a potential therapeutic strategy for mitigating M-I/R injury.
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