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

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.