Upregulation of microRNA-22 contributes to myocardial ischemia-reperfusion injury by interfering with the mitochondrial function.

Mitochondrial oxidative damage is critically involved in cardiac ischemia reperfusion (I/R) injury. MicroRNA-22 (miR-22) has been predicted to potentially target sirtuin-1 (Sirt1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), both of which are known to provide protection against mitochondrial oxidative injury. The present study aims to investigate whether miR-22 is involved in the regulation of cardiac I/R injury by regulation of mitochondrial function. We found that miR-22 level was significantly increased in rat hearts subjected to I/R injury, as compared with the sham group. Intra-myocardial injection of 20 ug miR-22 inhibitor reduced I/R injury as evidenced by significant decreases in cardiac infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels and the number of apoptotic cardiomyocytes. H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R) insult exhibited an increase in miR-22 expression, which was blocked by reactive oxygen species (ROS) scavenger and p53 inhibitor. In addition, miR-22 inhibitor attenuated, whereas miR-22 mimic aggravated H/R-induced injury in H9c2 cardiomyocytes. MiR-22 inhibitor per se had no significant effect on cardiac mitochondrial function. Mitochondria from rat receiving miR-22 inhibitor 48h before ischemia were found to have a significantly less mitochondrial superoxide production and greater mitochondrial membrane potential and ATP production as compared with rat receiving miR control. In H9c2 cardiomyocyte, it was found that miR-22 mimic aggravated, whilst miR-22 inhibitor significantly attenuated H/R-induced mitochondrial damage. By using real time PCR, western blot and dual-luciferase reporter gene analyses, we identified Sirt1 and PGC1α as miR-22 targets in cardiomyocytes. It was found that silencing of Sirt1 abolished the protective effect of miR-22 inhibitor against H/R-induced mitochondrial dysfunction and cell injury in cardiomyocytes. Taken together, our findings reveal a novel molecular mechanism for cardiac mitochondrial dysfunction during myocardial I/R injury at the miRNA level and demonstrate the therapeutic potential of miR-22 inhibition for acute myocardial I/R injury by maintaining cardiac mitochondrial function.

Du JK ，Cong BH ，Yu Q ，Wang H ，Wang L ，Wang CN ，Tang XL ，Lu JQ ，Zhu XY ，Ni X ... -  《-》

Inhibiting MicroRNA-29a Protects Myocardial Ischemia-Reperfusion Injury by Targeting SIRT1 and Suppressing Oxidative Stress and NLRP3-Mediated Pyroptosis Pathway.

Ding S ，Liu D ，Wang L ，Wang G ，Zhu Y ... -  《-》

Down-regulating miR-217-5p Protects Cardiomyocytes against Ischemia/Reperfusion Injury by Restoring Mitochondrial Function via Targeting SIRT1.

Qi Y ，Zhang K ，Li P ，Wu Z ... -  《-》

lncRNA Oip5-as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR-29a to activate the SIRT1/AMPK/PGC1α pathway.

Myocardial ischaemia/reperfusion (MI/R) injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanisms underlying MI/R injury are unclear. This study investigated the role of long non-coding RNA (lncRNA) Oip5-as1 in regulating mitochondria-mediated apoptosis during MI/R injury. Sprague-Dawley rats were subjected to MI/R induced by ligation of the left anterior descending coronary artery followed by reperfusion. H9c2 cells were incubated under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic in vivo MI/R. RT-qPCR and Western blot were used to evaluate gene and protein levels. CCK-8 assay, biochemical assay and flow cytometric analysis were performed to assess the function of Oip5-as1. The dual-luciferase gene reporter assay and RIP assay were conducted as needed. Oip5-as1 expression was downregulated in the hearts of rats with MI/R and in H9c2 cells treated with OGD/R. Oip5-as1 overexpression alleviated reactive oxygen species-driven mitochondrial injury and consequently decreased apoptosis in MI/R rats and H9c2 cells exposed to OGD/R. Mechanistically, Oip5-as1 acted as a competing endogenous RNA of miR-29a and thus decreased its expression. Inhibition of miR-29a reduced the oxidative stress and cytotoxicity induced by OGD/R. Overexpression of miR-29a reversed the anti-apoptotic effect of Oip5-as1 in H9c2 cells treated with OGD/R. Further experiments identified SIRT1 as a downstream target of miR-29a. Oip5-as1 upregulated SIRT1 expression and activated the AMPK/PGC1α pathway by targeting miR-29a, thus reducing the apoptosis triggered by OGD/R. However, these effects were reversed by a selective SIRT1 inhibitor, EX527. Oip5-as1 suppresses miR-29a leading to activation of the SIRT1/AMPK/PGC1α pathway, which attenuates mitochondria-mediated apoptosis during MI/R injury. Our findings thus provide new insights into the molecular mechanisms of MI/R injury.

Niu X ，Pu S ，Ling C ，Xu J ，Wang J ，Sun S ，Yao Y ，Zhang Z ... -  《-》

Upregulation of microRNA-34a enhances myocardial ischemia-reperfusion injury via the mitochondrial apoptotic pathway.

Li QH ，Ge ZW ，Xiang Y ，Tian D ，Tang Y ，Zhang YC ... -  《-》