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This study aims to investigate the role and underlying mechanism of ferroptosis in high\u2010salt (HS)\u2010induced myocardial damage. Our results reveal that HS stimulation inhibited cell proliferation and promoted apoptosis in cardiomyocyte HL\u20101 cells in a dose\u2010dependent manner. Ferroptotic features were observed in HS\u2010induced HL\u20101 cells, including ferric iron accumulation, decreased glutathione levels, increased oxidative stress levels, upregulation of ferroptosis marker proteins PTGS2, 4HNE and FTH1 and downregulation of GPX4, all of which were reversed by treatment with the ferroptosis suppressor Fer\u20101. Furthermore, the administration of Fer\u20101 ameliorated HS\u2010induced ferroptosis and myocardial damage in salt\u2010sensitive Dahl SS rats. Additionally, we found that a HS diet suppressed the SIRT1\/Nrf2 signalling pathway activation in our in\u00a0vivo experiments. Activation of SIRT1\/Nrf2 signalling by SIRT1 overexpression significantly attenuated ferroptosis in HS\u2010induced HL\u20101 cells. In conclusion, our findings demonstrate that HS levels induce myocardial injury by promoting ferroptosis via the deactivation of the SIRT1\/Nrf2 signalling pathway, highlighting the potential for therapeutic targeting of ferroptosis for hypertension\u2010related cardiovascular disorders.<\/jats:p>","DOI":"10.1111\/1440-1681.70016","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T06:36:27Z","timestamp":1735540587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High Salt Exacerbates Myocardial Dysfunction In\u00a0Vitro and In\u00a0Vivo by Promoting <scp>SIRT1<\/scp>\/Nrf2\u2010Mediated Ferroptosis"],"prefix":"10.1111","volume":"52","author":[{"given":"Wu","family":"Guanji","sequence":"first","affiliation":[{"name":"Department of Cardiology Xi'an Central Hospital  Xi'an 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