{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T17:20:18Z","timestamp":1777742418021,"version":"3.51.4"},"reference-count":0,"publisher":"Cell Physiol Biochem Press GmbH and Co KG","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"abstract":"<jats:p>Background\/Aims: Myocardial infarction (MI) remains the leading cause of cardiovascular morbidity and mortality. Although reperfusion therapy restores myocardial blood flow, it also induces myocardial ischemia-reperfusion injury (MI\/RI), which worsens prognosis. Ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid reactive oxygen species (ROS), plays a central role in MI\/RI. This process is characterized by a downregulation of glutathione peroxidase 4 (GPX4) and an upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). While long non-coding RNA (lncRNA) ANRIL has been found to be aberrantly expressed in acute myocardial infarction (AMI) and is believed to provide myocardial protection, its role and underlying mechanism in MI\/RI-induced ferroptosis remain unclear. Methods: A mouse MI\/R model was established by ligating the left anterior descending (LAD) coronary artery in C57BL\/6 mice. In parallel, HL-1 and H9C2 cardiomyocytes underwent hypoxia-reoxygenation (H\/R) to simulate MI\/RI in vitro. Lnc-ANRIL was either overexpressed using the pEGFP-lnc-ANRIL plasmid or silenced with an siRNA targeting ANRIL (siANRIL). Ferroptosis indicators, including ROS, malondialdehyde (MDA), Fe\u00b2\u207a, GPX4, and ACSL4, were assessed. Potential microRNAs (miRNAs) targeting lnc-ANRIL and GPX4 were predicted by microRNA Target Prediction Database (miRDB) and validated through dual-luciferase assays. Results: In both MI\/R mouse myocardial tissue and H\/R-treated cardiomyocytes, ferroptosis was activated, as evidenced by downregulated GPX4, upregulated ACSL4, and increased levels of ROS, MDA, and Fe\u00b2\u207a. Concurrently, lnc-ANRIL expression was reduced. Overexpression of lnc-ANRIL attenuated H\/R-induced ferroptosis, reduced cell death and ferroptosis markers, and upregulated GPX4 expression. Conversely, silencing lnc-ANRIL exacerbated ferroptosis. Mechanistically, lnc-ANRIL acted as a sponge for miR-7238-3p, which targets the 3'-UTR of GPX4 to suppress its expression. Overexpression of miR-7238-3p mimicked the ferroptosis phenotype associated with low lnc-ANRIL expression and exacerbated cardiomyocyte damage. Conclusion: MI\/RI downregulates lnc-ANRIL, thereby relieving the inhibition of miR-7238-3p. This, in turn, suppresses GPX4 expression and triggers ferroptosis in cardiomyocytes. Lnc-ANRIL protects against MI\/RI-induced ferroptosis through the miR-7238-3p\/GPX4 axis, identifying a potential novel therapeutic target for ischemic heart disease.<\/jats:p>","DOI":"10.33594\/000000837","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T08:16:56Z","timestamp":1767169016000},"page":"903-917","source":"Crossref","is-referenced-by-count":2,"title":["Lnc-ANRIL Protects Against Myocardial Ischemia-Reperfusion Injury by Suppressing Ferroptosis via the miR-7238-3p\/GPX4 Axis"],"prefix":"10.33594","volume":"59","author":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong, China","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijun","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binhua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Anesthesiology of the Affiliated Hospital, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524000, Guangdong, China","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Guangdong Zhanjiang Marine Biomedical Research Institute, Zhanjiang, 524000, China","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Department of Anesthesiology of the Affiliated Hospital, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524000, Guangdong, China","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guixi","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"19235","published-online":{"date-parts":[[2025,12,31]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T08:16:57Z","timestamp":1767169017000},"score":1,"resource":{"primary":{"URL":"https:\/\/cellphysiolbiochem.com\/Articles\/000837\/index.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,31]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,12,31]]}},"URL":"https:\/\/doi.org\/10.33594\/000000837","relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,31]]}}}