{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T12:24:38Z","timestamp":1793622278038,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Mice with cardiomyocyte\u2010specific deletion of Bmal1, a core clock gene, had spontaneous abnormal cardiac metabolism, dilated cardiomyopathy, and shortened lifespan. However, the role of cardiomyocyte Bmal1 in pressure overload induced cardiac remodeling is unknown. Here we aimed to understand the contribution of cardiomyocyte Bmal1 to cardiac remodeling in response to pressure overload induced by transverse aortic constriction or chronic angiotensin \u2161 (Ang\u2161) infusion.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">By generating a tamoxifen\u2010inducible cardiomyocyte\u2010specific Bmal1 knockout mouse line (cKO) and challenging the mice with transverse aortic constriction or Ang\u2161, we found that compared to littermate controls, the cKO mice displayed remarkably increased cardiac hypertrophy and augmented fibrosis both after transverse aortic constriction and Ang\u2161 induction, as assessed by echocardiographic, gravimetric, histologic, and molecular analyses. Mechanistically, RNA\u2010sequencing analysis of the heart after transverse aortic constriction exposure revealed that the PI3K\/AKT signaling pathway was significantly activated in the cKOs. Consistent with the in vivo findings, in vitro study showed that knockdown of Bmal1 in cardiomyocytes significantly promoted phenylephrine\u2010induced cardiomyocyte hypertrophy and triggered fibroblast\u2010to\u2010myofibroblast differentiation, while inhibition of AKT remarkedly reversed the pro\u2010hypertrophy and pro\u2010fibrosis effects of Bmal1 knocking down.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These results suggest that postnatal deletion of Bmal1 in cardiomyocytes may promote pressure overload\u2010induced cardiac remodeling. Moreover, we identified PI3K\/AKT signaling pathway as the potential mechanistic ties between Bmal1 and cardiac remodeling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.025021","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T10:32:03Z","timestamp":1655893923000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Postnatal Deletion of Bmal1 in Cardiomyocyte Promotes Pressure Overload Induced Cardiac Remodeling in Mice"],"prefix":"10.1161","volume":"11","author":[{"given":"Qing","family":"Liang","sequence":"first","affiliation":[{"name":"Advanced Institute for Medical Sciences Dalian Medical University Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-0932","authenticated-orcid":false,"given":"Hu","family":"Xu","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences Dalian 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