Dataset Information

Ischemic Postconditioning Protects against Aged Myocardial Ischemia/Reperfusion Injury by Transcriptional and Epigenetic Regulation of miR-181a-2-3p.

ABSTRACT: Ischemic postconditioning (IPostC) has been proposed as a strategy to mitigate the risk of ischemia/reperfusion (I/R) injury, and autophagy is involved in I/R-induced aged myocardial injury, while the underlying mechanism of IPostC-regulated autophagy is unknown. Here, we implemented miRNA sequencing analysis in aged cardiomyocytes to identify a novel miR-181a-2-3p after HPostC, which inhibits autophagy by targeting AMBRA1 in aged myocardium to protect I/R-induced aged myocardial injury. Mechanistically, we identified that IPostC can induce DNA hypomethylation and H3K14 hyperacetylation of miR-181a-2-3p promoter due to the decreased binding of DNMT3b and HDAC2 at its promoter, which contributes to enhancing the expression of miR-181a-2-3p. More importantly, cooperation of DNMT3b and HDAC2 inhibits the binding of c-Myc at the miR-181a-2-3p promoter in aged cardiomyocytes. In summary, IPostC attenuates I/R-induced aged myocardial injury through upregulating miR-181a-2-3p expression, which is an attribute to transcriptional and epigenetic regulation of its promoter. Our data indicate that miR-181a-2-3p may be a potential therapeutic target against I/R injury in aged myocardium.

SUBMITTER: Li G

PROVIDER: S-EPMC9155916 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Ischemic Postconditioning Protects against Aged Myocardial Ischemia/Reperfusion Injury by Transcriptional and Epigenetic Regulation of miR-181a-2-3p.

Li Guizhong G Ding Ning N Xiong Jiantuan J Ma Shengchao S Xie Lin L Xu Lingbo L Zhang Hui H Yang Anning A Yang Yong Y Jiang Yideng Y Zhang Huiping H

Oxidative medicine and cellular longevity 20220524

Ischemic postconditioning (IPostC) has been proposed as a strategy to mitigate the risk of ischemia/reperfusion (I/R) injury, and autophagy is involved in I/R-induced aged myocardial injury, while the underlying mechanism of IPostC-regulated autophagy is unknown. Here, we implemented miRNA sequencing analysis in aged cardiomyocytes to identify a novel miR-181a-2-3p after HPostC, which inhibits autophagy by targeting AMBRA1 in aged myocardium to protect I/R-induced aged myocardial injury. Mechani ...[more]

PMID: 35656020

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Project description:Ischemic postconditioning (IPoC) has been demonstrated to prevent myocardial ischemia?reperfusion injury (MIRI), but its cardioprotective effect is abrogated by hypercholesterolemia. The aim of the present study was to determine whether lycopene (LP), a type of carotenoid, can restore the cardioprotective effect of IPoC in hypercholesterolemic rats. Male Wistar rats were fed a cholesterol?enriched diet for 12 weeks to establish a hypercholesterolemic model. The rat hearts were isolated and subjected to 30 min ischemia and 60 min reperfusion using a Langendorff apparatus. LP was administered to the rats intraperitoneally for 5 consecutive days prior to ischemia and reperfusion. Myocardial pathological changes, infarct size and cell apoptosis were measured by hematoxylin and eosin, triphenyltetrazolium chloride and TUNEL staining, respectively. The changes in endoplasmic reticulum (ER) stress markers, the reperfusion injury salvage kinase (RISK) pathway and mitochondrial apoptosis?related proteins were detected by western blotting. Overall, the results demonstrated that low?dose LP in combination with IPoC ameliorated myocardial histopathological changes, reduced the infarct size and release of cardiac enzymes, and decreased cardiomyocyte apoptosis in hypercholesterolemic rats, but no beneficial effects were achieved by the same dose of LP or IPoC treatment were used alone. Furthermore, the combination of LP and IPoC inhibited the expression of glucose?regulated protein 78 and C/EBP homologous protein, increased the phosphorylation levels of AKT, ERK1/2 and glycogen synthase kinase?3?, repressed mitochondrial permeability transition pore opening, and reduced the expression of cytochrome c, cleaved caspase?9 and cleaved caspase?3. Collectively, these findings demonstrated that LP can restore the cardioprotective effects of IPoC on MIRI in hypercholesterolemic rats, and this restoration by LP was mediated by inhibition of ER stress and reactivation of the RISK pathway in hypercholesterolemic rat myocardium.

Dataset Information

Ischemic Postconditioning Protects against Aged Myocardial Ischemia/Reperfusion Injury by Transcriptional and Epigenetic Regulation of miR-181a-2-3p.

Publications

Ischemic Postconditioning Protects against Aged Myocardial Ischemia/Reperfusion Injury by Transcriptional and Epigenetic Regulation of miR-181a-2-3p.

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