Abstract
ObjectivesMyocardial 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 methodsSprague‐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.ResultsOip5‐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.ConclusionsOip5‐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.
Highlights
Acute myocardial infarction (AMI) causes high morbidity and mortality worldwide.[1]
Our pilot analysis showed that both Oip5-as[1] and miR-29a are deregulated in a rat model with myocardial ischaemia/reperfusion (MI/R) injury
We evaluated the role of miR-29a in oxidative stress injury under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. miR-29a was significantly upregulated in neonatal rat ventricular myocytes (NRVMs), and H9c2 cells treated with OGD/R (Figure 5A)
Summary
Acute myocardial infarction (AMI) causes high morbidity and mortality worldwide.[1]. Currently, myocardial reperfusion by thrombolytic therapy or percutaneous coronary intervention is the most effective approach for AMI treatment.[2]. OIP5-AS1 (Opa-interacting protein 5-antisense transcript 1) was first identified as the mammalian homolog of the zebrafish transcript cyrano during analyses of the zebrafish and human transcriptomes.[12] OIP5-AS1 is an evolutionarily conserved lncRNA and is predominantly expressed in the cytoplasm.[12,13] OIP5-AS1 is reported to be a key regulator in tumour growth and progression.[14,15,16,17,18] For example, OIP5-AS1 downregulation inhibits breast cancer progression by targeting SOX2 (sex-determining region Y-box 2) via miR-129-5p upregulation.[14] OIP5-AS1 promotes glioma oncogenesis by sponging miR-367-3p to modulate the expression of CEBPA (CCAAT/enhancer binding protein alpha).[16] the role of OIP5-AS1 in myocardial apoptosis following MI/R injury is unknown. We showed for the first time that Oip5-as[1] sponged miR-29a to upregulate the expression of SIRT1, which activated the AMPK/PGC1α (AMP-activated protein kinase/peroxisome proliferator-activated receptor γ coactivator 1 alpha) signalling pathway to attenuate MI/R injury
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
