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Changes in cardiac pathology after myocardial infarction (MI) were analyzed with hematoxylin-eosin staining. Myocardial cell apoptosis in the heart tissues of rats with MI was assessed using TUNEL staining. In H\/R-induced H9C2 cells, cell viability and lactate dehydrogenase (LDH) and adenosine 5\u2019-triphosphate levels were detected. Apoptosis and MMP in H9C2 cells were detected with flow cytometry. Our results demonstrated that IIM treatment reduced myocardial injury induced by ischemia-reperfusion (I\/R) and suppressed cardiomyocyte apoptosis, inflammation, and autophagy induced by I\/R in rats. Moreover, we confirmed that IIM repressed apoptosis and regulated MMP in H9C2 cells exposed to H\/R. IIM relieved the inflammatory response and autophagy in H\/R-treated H9C2 cells. In addition, IIM inhibited the Kr\u00fcpple-like factor 4 (KLF4)\/NF-\u03baB pathway in H\/R-induced H9C2 cells. Interestingly, the function of IIM on apoptosis, MMP, inflammation and autophagy were abolished by KLF4 overexpression in H\/R-induced H9C2 cells. In conclusion, IIM could repress cardiomyocyte apoptosis, inflammation and autophagy through the inhibition of the KLF4\/NF-\u03baB pathway and thus reduced myocardial injury <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0323247","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:29:17Z","timestamp":1749144557000},"page":"e0323247","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The protective effect of iron isomaltoside on myocardial ischemia-reperfusion injury via the suppression of KLF4\/NF-\u03baB signaling"],"prefix":"10.1371","volume":"20","author":[{"given":"Huiping","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duanchen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghua","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-5818","authenticated-orcid":true,"given":"Qiaofeng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0430-9331","authenticated-orcid":true,"given":"Aixia","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"issue":"3","key":"pone.0323247.ref001","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2174\/1871525714666161216100553","article-title":"Pathophysiology 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