Key result
Administration of a miR-146a mimic preserved cardiac function and reduced infarction area and fibrosis in a mouse model of myocardial ischaemia reperfusion injury by inhibiting NOX4 signalling.
Why the study?
Although miR-146a is implicated in cardiovascular diseases, its functional role and underlying mechanism in myocardial ischaemia reperfusion injury remained unclear.
Does miR-146a mimic reduce myocardial ischaemia reperfusion injury in mouse and cell models?
Does miR-146a mimic reduce myocardial ischaemia reperfusion injury in mouse and cell models?
The miR-146a mimic protects against myocardial ischaemia reperfusion injury by inhibiting NOX4/P38 signalling in preclinical models, suggesting a potential therapeutic target.
Evidence suggests that miR-146a is implicated in the pathogenesis of cardiovascular diseases; however, the role of miR-146a in myocardial ischaemia reperfusion (I/R) injury is unclear. The aim of this study was to explore the functional role of miR-146a in myocardial ischaemia reperfusion injury and the underlying mechanism. C57BL/6J mice were subjected to 45 min of ischaemia and 1 week of reperfusion to establish a myocardial I/R injury model. A miR-146a mimic (0.5 mg/kg) was administered intravenously at the beginning of the ischaemia process. Neonatal rat cardiomyocytes were also subjected to hypoxia/reperfusion (H/R). Cells were treated with the miR-146a mimic or antagonist. As a result, the miR-146a mimic attenuated H/R-induced cardiomyocyte injury, as evidenced by increased cell viability and reduced lactate dehydrogenase (LDH) levels. In addition, the miR-146a mimic inhibited oxidative stress in cells suffering from H/R injury. Moreover, the miR-146a antagonist exerted adverse effects in vitro. In mice with myocardial I/R injury, the miR-146a mimic preserved cardiac function and reduced the infarction area and fibrosis. Moreover, the miR-146a mimic decreased the inflammatory response and reactive oxygen species (ROS) accumulation in mouse hearts. Mechanistically, we found that miR-146a directly regulated the transcription of NOX4, which subsequently affected P38 signalling in cardiomyocytes. When we knocked down NOX4, the effects of the miR-146a antagonist in worsening the cell condition were counteracted in in vitro experiments. Taken together, the results suggest that miR-146a protects against myocardial ischaemia reperfusion injury by inhibiting NOX4 signalling. The miR-146a mimic may become a potential therapeutic approach for patients with myocardial ischaemia reperfusion.
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Xiao et al. (2021) studied Myocardial ischaemia reperfusion (I/R) injury. miR-146a mimic was evaluated on Cardiomyocyte injury, cardiac function, infarction area, and fibrosis. Administration of a miR-146a mimic preserved cardiac function and reduced infarction area and fibrosis in a mouse model of myocardial ischaemia reperfusion injury by inhibiting NOX4 signalling.
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