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Carnosol, a phenolic compound extracted from rosemary, possesses noteworthy pharmacological properties including anti\u2010inflammatory, antioxidant, and anti\u2010apoptotic activities. Considering the pivotal involvement of inflammation, oxidative stress, and apoptosis in cardiac remodeling, the present study aims to assess the effects of carnosol on cardiac remodeling and elucidate the underlying mechanisms. In an in vivo model, cardiac remodeling was induced by performing transverse aortic constriction (TAC) surgery on mice, while an in vitro model was established by treating neonatal rat cardiomyocytes (NRCMs) with Ang II. Our results revealed that carnosol treatment effectively ameliorated TAC\u2010induced myocardial hypertrophy and fibrosis, thereby attenuating cardiac dysfunction in mice. Moreover, carnosol improved cardiac electrical remodeling and restored connexin 43 expression, thereby reducing the vulnerability to ventricular fibrillation (VF). Furthermore, carnosol significantly reduced Ang II\u2010induced cardiomyocyte hypertrophy in NRCMs and alleviated the upregulation of hypertrophy and fibrosis markers. Both in vivo and in vitro models of cardiac remodeling exhibited the anti\u2010inflammatory, anti\u2010oxidative, and anti\u2010apoptotic effects of carnosol. Mechanistically, these effects were mediated through the Sirt1\/PI3K\/AKT pathway, as the protective effects of carnosol were abrogated upon inhibition of Sirt1 or activation of the PI3K\/AKT pathway. In summary, our study suggests that carnosol prevents cardiac structural and electrical remodeling by regulating the anti\u2010inflammatory, anti\u2010oxidative, and anti\u2010apoptotic effects mediated by Sirt1\/PI3K\/AKT signaling pathways, thereby alleviating heart failure and VF.<\/jats:p>","DOI":"10.1002\/ptr.8213","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T06:15:37Z","timestamp":1717481737000},"page":"3763-3781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload\u2010induced heart failure mice"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9861-5223","authenticated-orcid":false,"given":"Zhao","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan 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