{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T16:10:17Z","timestamp":1778343017076,"version":"3.51.4"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"\n Background<\/jats:title>\n \n Adult cardiomyocytes are terminally differentiated with limited capacity for cell cycle re\u2010entry. However, recent studies have shown that cycling cardiomyocytes may exert cardioprotective effects after myocardial infarction (MI). The\n Myc<\/jats:italic>\n family\u2014\n Myc<\/jats:italic>\n ,\n Mycl<\/jats:italic>\n , and\n Mycn<\/jats:italic>\n \u2014regulates cell cycle progression and plasticity, raising the possibility that specific isoforms could reactivate cardiomyocyte cycling and therefore enhance cardiac repair in MI. This study evaluated the effects of\n Myc<\/jats:italic>\n isoforms on cardiomyocyte cell cycle activation and cardiac outcomes after MI.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Cardiomyocyte\u2010specific overexpression of\n Myc<\/jats:italic>\n ,\n Mycl<\/jats:italic>\n , or\n Mycn<\/jats:italic>\n was induced in adult mice using adeno\u2010associated virus 9 vectors driven by the cardiac troponin T promoter. Cell cycle activity, remodeling, and function were assessed by RNA sequencing, immunohistochemistry, and echocardiography. Cardioprotection was evaluated in MI models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Mycn<\/jats:italic>\n elicited the most robust cell cycle gene expression among the\n Myc<\/jats:italic>\n isoforms.\n Mycn<\/jats:italic>\n overexpression markedly enhanced cardiomyocyte re\u2010entry\u2014evidenced by increased 5\u2010bromo\u20102\u2032\u2010deoxyuridine incorporation and histone H3 phosphorylation\u2014and induced hypertrophic growth. Transcriptomic profiling revealed\n Mycn<\/jats:italic>\n \u2010specific upregulation of extracellular matrix and paracrine signaling genes, which are typically enriched in neonatal cardiomyocytes and also linked to cardioprotection. In MI models,\n Mycn<\/jats:italic>\n preserved cardiac contractility, reduced infarct size, and increased capillary density in peri\u2010infarct regions.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Mycn<\/jats:italic>\n exerts robust biological effects in the adult heart, including reactivation of the cardiomyocyte cell cycle and promotion of cardioprotection following ischemic injury. Its effects likely involve induction of a neonatal\u2010like transcriptional program that fosters a stress\u2010adaptive microenvironment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.125.046146","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:48:50Z","timestamp":1775728130000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Mycn<\/i>\n Reactivates the Cell Cycle in Adult Cardiomyocytes and Promotes Cardioprotection in Myocardial Infarction"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-1725","authenticated-orcid":false,"given":"Aina","family":"Hirofuji","sequence":"first","affiliation":[{"name":"Asahikawa Medical University","place":["Asahikawa, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"National Institutes of Biomedical Innovation","place":["Osaka, Japan"]},{"name":"Asahikawa Medical University","place":["Hokkaido, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1407-446X","authenticated-orcid":false,"given":"Yuki","family":"Tsujita","sequence":"additional","affiliation":[{"name":"Asahikawa Medical University","place":["Asahikawa, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1405-060X","authenticated-orcid":false,"given":"Ryo","family":"Okubo","sequence":"additional","affiliation":[{"name":"Asahikawa Medical University","place":["Asahikawa, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-5759","authenticated-orcid":false,"given":"Ryohei","family":"Ushioda","sequence":"additional","affiliation":[{"name":"Asahikawa Medical University","place":["Asahikawa, 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Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-5045","authenticated-orcid":false,"given":"Megumi","family":"Kanao\u2010Kanda","sequence":"additional","affiliation":[{"name":"Wakayama Medical University School of Medicine","place":["Wakayama, Japan"]},{"name":"Asahikawa Medical University","place":["Asahikawa, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1068-7024","authenticated-orcid":false,"given":"Yusuke","family":"Mizukami","sequence":"additional","affiliation":[{"name":"National Institutes of Biomedical Innovation","place":["Osaka, Japan"]},{"name":"Sapporo\u2010Higashi Tokushukai Hospital","place":["Sapporo, Japan"]},{"name":"Asahikawa Medical University","place":["Asahikawa, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Asahikawa Medical 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