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High levels of triiodothyronine (T3) induce cardiac hypertrophy, a risk factor for cardiac complications and heart failure. Previous results have demonstrated that angiotensin\u2010(1\u20107) is able to block T3\u2010induced cardiac hypertrophy; however, the molecular mechanisms involved in this event have not been fully elucidated. Here, we evidenced the contribution of FOXO3 signaling to angiotensin\u2010(1\u20107) effects. Angiotensin\u2010(1\u20107) treatment increased nuclear FOXO3 levels and reduced p\u2010FOXO3 levels (inactive form) in isolated cardiomyocytes. Knockdown of FOXO3 by RNA silencing abrogated the antihypertrophic effect of angiotensin\u2010(1\u20107). Increased expression of antioxidant enzymes superoxide dismutase 1 (SOD1 and catalase) and lower levels of reactive oxygen species and nuclear factor\u2010\u03baB (NF\u2010\u03baB) were observed after angiotensin\u2010(1\u20107) treatment in vitro. Consistent with these results, transgenic rats overexpressing angiotensin\u2010(1\u20107) displayed increased nuclear FOXO3 and SOD1 levels and reduced NF\u2010\u03baB levels in the heart. These results provide a new molecular mechanism responsible for the antihypertrophic effect of angiotensin\u2010(1\u20107), which may contribute to future therapeutic targets.<\/jats:p>","DOI":"10.1002\/jcp.30069","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T09:45:12Z","timestamp":1600854312000},"page":"3059-3072","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Angiotensin\u2010(1\u20107) prevents T3\u2010induced cardiomyocyte hypertrophy by upregulating FOXO3\/SOD1\/catalase and downregulating NF\u2010\u0138B"],"prefix":"10.1002","volume":"236","author":[{"given":"Nathalia","family":"Senger","sequence":"first","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences University of Sao Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4316-0218","authenticated-orcid":false,"given":"Aline","family":"C. 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