{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:00:07Z","timestamp":1793260807844,"version":"4.5.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,6,21]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Embryonic heart is characterized of rapidly dividing cardiomyocytes required to build a working myocardium. Cardiomyocytes retain some proliferative capacity in the neonates but lose it in adulthood. Consequently, a number of signaling hubs including microRNAs are altered during cardiac development that adversely impacts regenerative potential of cardiac tissue. Embryonic stem cell cycle miRs are a class of microRNAs exclusively expressed during developmental stages; however, their effect on cardiomyocyte proliferation and heart function in adult myocardium has not been studied previously.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To determine whether transient reintroduction of embryonic stem cell cycle miR-294 promotes cardiomyocyte cell cycle reentry enhancing cardiac repair after myocardial injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              miR-294 is expressed in the heart during development, prenatal stages, lost in the neonate, and adult heart confirmed by qRT-PCR and in situ hybridization. Neonatal ventricular myocytes treated with miR-294 showed elevated expression of Ki67, p-histone H3, and Aurora B confirmed by immunocytochemistry compared with control cells. miR-294 enhanced oxidative phosphorylation and glycolysis in Neonatal ventricular myocytes measured by seahorse assay. Mechanistically, miR-294 represses\n              <jats:italic>Wee1<\/jats:italic>\n              leading to increased activity of the\n              <jats:italic>cyclin B1\/CDK1<\/jats:italic>\n              complex confirmed by qRT-PCR and immunoblot analysis. Next, a doxycycline-inducible AAV9-miR-294 vector was delivered to mice for activating miR-294 in myocytes for 14 days continuously after myocardial infarction. miR-294\u2013treated mice significantly improved left ventricular functions together with decreased infarct size and apoptosis 8 weeks after MI. Myocyte cell cycle reentry increased in miR-294 hearts analyzed by Ki67, pH3, and AurB (Aurora B kinase) expression parallel to increased small myocyte number in the heart. Isolated adult myocytes from miR-294 hearts showed increased 5-ethynyl-2\u2032-deoxyuridine+ cells and upregulation of cell cycle markers and miR-294 targets 8 weeks after MI.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Ectopic transient expression of miR-294 recapitulates developmental signaling and phenotype in cardiomyocytes promoting cell cycle reentry that leads to augmented cardiac function in mice after myocardial infarction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.118.314223","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T14:48:22Z","timestamp":1554821302000},"page":"14-25","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":102,"title":["Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Cycle Reentry After Injury"],"prefix":"10.1161","volume":"125","author":[{"given":"Austin","family":"Borden","sequence":"first","affiliation":[{"name":"From the Center for Metabolic Disease Research (A.B., J.K., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Kurian","sequence":"additional","affiliation":[{"name":"From the Center for Metabolic Disease Research (A.B., J.K., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Nickoloff","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine (E.N., J.I., A.M.L., E.G., W.J.K., R.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Yang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (Y.Y., C.D.T., S.M., 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