MiR-703 protects against hypoxia/reoxygenation-induced cardiomyocyte injury via inhibiting the NLRP3/caspase-1-mediated
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MiR-703 protects against hypoxia/reoxygenation-induced cardiomyocyte injury via inhibiting the NLRP3/caspase-1-mediated pyroptosis Xiaoliang Wei 1 & Hu Peng 1 & Ming Deng 2 & Zongming Feng 2 & Changnong Peng 2 & Dahao Yang 2 Received: 17 January 2020 / Accepted: 1 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Myocardial infarction represents one of the severe cardiovascular diseases and is one of the high-risk factors for mortality, and ischemia/reperfusion (I/R) injury is one of the risk factors that contribute to the high mortality of myocardial infarction. MicroRNAs have been proven as key regulators in various diseases including myocardial infarction. The present study was sought to determine the role of miR-703 in the myocardial I/R injury and to explore detailed mechanisms. Hypoxia/ reoxygenation (H/R) treatment repressed cell viability, increased cytotoxicity and pyroptosis in mouse cardiomyocytes. More importantly, we found that miR-703 was suppressed in mouse cardiomyocytes upon H/R stimulation. Restoration of miR-703 expression in mouse cardiomyocytes counteracted the H/R-induced cytotoxicity and pyroptosis in mouse cardiomyocytes; and the effects of miR-703 inhibition on cell viability and pyroptosis were similar to that of H/R treatment in mouse cardiomyocytes. In a further investigation, we found that NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) was targeted and repressed by miR-703 in mouse cardiomyocytes. NLRP3 knockdown also attenuated H/R-induced cytotoxicity and pyroptosis in mouse cardiomyocytes. In the mechanistic perspective, NLRP3 enforced expression disrupted the protective effects of miR703 restoration on the H/R-induced cytotoxicity and pyroptosis in mouse cardiomyocytes. Our results for the first time demonstrate the protective actions of miR-703 in the H/R-induced mouse cardiomyocyte injury. More importantly, miR-703 protects against H/R-induced cardiomyocyte injury via inhibiting the NLRP3/caspase-1-mediated pyroptosis. Keywords Ischemia/reperfusion . Hypoxia/reoxygenation . Mouse cardiomyocytes . miR-703 . Pyroptosis . NLRP3
Xiaoliang Wei and Hu Peng contributed equally to this work. * Changnong Peng [email protected] * Dahao Yang [email protected] Xiaoliang Wei [email protected] Hu Peng [email protected] Ming Deng [email protected] Zongming Feng [email protected] 1
The Center of Cardiovascular Diseases, the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China
2
Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen Sun Yat-sen Cardiovascular Hospital, Shenzhen 518057, China
Introduction Myocardial infarction represents one of the severe cardiovascular diseases and is one of the high-risk factors for mortality (Lu et al., 2015). In the process of myocardial infarction, the restoration of blood flow can lead to more serious injury, which results in impaired cardiac function and increased mortality, and this phenomenon is referred as ischemia/ reperfusio
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