CircularRNA CRIRTM alleviates myocardial ischemia-reperfusion injury by inhibiting the combination of microRNA-1 and calmodulin
South China Journal of Cardiology(2021)
Abstract
Background Myocardial ischemia/reperfusion(I/R) injury remains a great challenge in clinical therapy.Recent studies indicated that circularRNA(circRNA) play an important role in the regulation of atherosclerotic heart disease.However, as a new circRNA, the effect of circRNA regulating ischemia-reperfusion through microRNA-1(CRIRTM) on myocardial apoptosis during myocardial ischemia/reperfusion is still unknown.The purpose of this study was to investigate the effect of CRIRTM on I/R-induced apoptosis and the expression of microRNA-1(miR-1) and calmodulin(CaM) in cultured neonatal rat ventricular cardiomyocytes(NRVCs) in vitro and SD rat hypoxia-reoxygenation model in vivo.Methods NRVCs were subjected to hypoxia for 30 minutes and then oxygen was added for 12 hours to establish the model of cell ischemia reperfusion.The SD rats were subjected to the surgery of ligating the anterior descending branch of the left coronary artery for 4 hours and then reperfused for 48 hours to establish myocardial ischemia animal model.The expression of CRIRTM, miIR-1 and CaM was detected by quantitative real-time polymerase chain reaction(qRT-PCR).TUNEL was used to analyze the apoptosis level of cells and animal myocardium after small interfering RNA(siRNA) down-regulation of CRIRTM.The expression of CRIRTM in the blood of patients with myocardial infarction was detected, and the downstream of CRIRTM was analyzed by Target Scan.Results The specific upregulation of CRIRTM was detected in the plasma of patients with ST-segment elevation myocardial infarction after reperfusion, and multiple binding sites between CRIRTM and miR-1 were found by Target Scan analysis.The expression of CRIRTM and CaM was up-regulated and the expression of miR-1 was down-regulated in cells and rats I/R model.Both in vivo and in vitro, cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion will increase after down-regulation of CRIRTM.It may be due to the decreased inhibition of miR-1 by down-regulated CRIRTM, which increases the degradation of CaM by miR-1 and aggravates cardiomyocyte apoptosis.Conclusions Our data demonstrated that CRIRTM alleviates myocardial ischemia-reperfusion injury via suppressing miR-1 leading to enhanced CaM levels.[S Chin J Cardiol 2021;22(1):30-37]
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Key words
circRNA regulating ischemia-reperfusion through microRNA-1 (CRIRTM),miR-1,myocardial ischemia-reperfusion,calmodulin
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