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Here, we implemented miRNA sequencing analysis in aged cardiomyocytes to identify a novel miR\u2010181a\u20102\u20103p after HPostC, which inhibits autophagy by targeting AMBRA1 in aged myocardium to protect I\/R\u2010induced aged myocardial injury. Mechanistically, we identified that IPostC can induce DNA hypomethylation and H3K14 hyperacetylation of miR\u2010181a\u20102\u20103p promoter due to the decreased binding of DNMT3b and HDAC2 at its promoter, which contributes to enhancing the expression of miR\u2010181a\u20102\u20103p. More importantly, cooperation of DNMT3b and HDAC2 inhibits the binding of c\u2010Myc at the miR\u2010181a\u20102\u20103p promoter in aged cardiomyocytes. In summary, IPostC attenuates I\/R\u2010induced aged myocardial injury through upregulating miR\u2010181a\u20102\u20103p expression, which is an attribute to transcriptional and epigenetic regulation of its promoter. Our data indicate that miR\u2010181a\u20102\u20103p may be a potential therapeutic target against I\/R injury in aged myocardium.<\/jats:p>","DOI":"10.1155\/2022\/9635674","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T22:35:07Z","timestamp":1653431707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ischemic Postconditioning Protects against Aged Myocardial Ischemia\/Reperfusion Injury by Transcriptional and Epigenetic Regulation of 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