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However, the opening of the \u2018culprit artery\u2019 is accompanied by myocardial ischemia\u2013reperfusion injury (IRI), partially offsetting the benefits of revascularisation. At present, effective methods to alleviate myocardial IRI are lacking. Cardiomyocyte ferritinophagy induces myocardial ferroptosis and IRI. In the present study, the RT\u2010PCR, western blotting, co\u2010immunoprecipitation, and immunofluorescence co\u2010localisation experiments revealed that hypoxia\u2010reoxygenation (H\/R) of cardiomyocytes induces the dephosphorylation of Mst1 at Thr183, a crucial autophagy inhibitory site. Its dephosphorylation impairs the phosphorylation of Beclin1 at Ser295, thereby potentiating ferritinophagy, triggering ferroptosis and exacerbating H\/R\u2010induced cardiomyocyte injury. In addition, valsartan restored the phosphorylation of Mst1 at Thr183 and Beclin1 at Ser295, thereby inhibiting myocardial ferritinophagy and ferroptosis. Valsartan also inhibits cardiomyocyte ferritinophagy by blocking the angiotensin II type 1 receptor. In\u00a0vivo, valsartan ameliorated myocardial ferritinophagy, ferroptosis and IRI. However, following treatment with a ferroptosis inhibitor, valsartan failed to further alleviate myocardial IRI. In cardiomyocyte\u2010specific Mst1 knockout mice, valsartan failed to suppress myocardial ferritinophagy and ferroptosis, and consequently showed no therapeutic efficacy against IRI. Pre\u2010revascularisation administration of valsartan attenuated revascularisation\u2010induced myocardial injury and improved cardiac function in patients with AMI. These findings suggest that valsartan may mitigate myocardial IRI and improve clinical outcomes in patients with AMI by regulating the AT\n                      <jats:sub>1<\/jats:sub>\n                      R\/Mst1\/Beclin1 axis, thus inhibiting myocardial ferritinophagy and ferroptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>The Chinese Clinical Trial Registry (TRN ChiCTR2100043501)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jcmm.71269","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:37:28Z","timestamp":1783060648000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Valsartan Reduces Myocardial Ischemia\u2013Reperfusion Injury by Inhibiting Ferritinophagy\u2010Mediated 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