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Circular RNAs (circRNAs) play an important role in cardiovascular disease. In this study we investigated the regulatory role of circDhx32 in the progression of I\/R injury. Cardiac I\/R model was established in mice by ligating the left anterior descending coronary artery (LAD) for 45\u2009min, followed by blood reperfusion for 24\u2009h or 2 weeks. For in vitro study, neonatal mouse ventricular cardiomyocytes were subjected to hypoxia-reoxygenation (H\/R) assault. CircDhx32 was significantly upregulated in I\/R-treated mice and H\/R-treated cardiomyocytes. Cardiomyocyte-specific knockdown of circDhx32 ameliorated the pathological outcomes of cardiac I\/R injury including improved cardiac function, reduced infarct size and reduced release of cardiac injury biomarkers. The protective effects of circDhx32 silencing were also observed in cardiomyocytes after H\/R. We demonstrated that ALKBH5 functioned as an m\n                    <jats:sup>6<\/jats:sup>\n                    A demethylase, removing the m\n                    <jats:sup>6<\/jats:sup>\n                    A modification sites of circDhx32. Reduced m\n                    <jats:sup>6<\/jats:sup>\n                    A modification inhibited recognition and bindin\n                    <jats:underline>g<\/jats:underline>\n                    by the m\n                    <jats:sup>6<\/jats:sup>\n                    A readers YTHDF2 and YTHDC1, leading to circDhx32 degradation and diminished nucleoplasmic export under pathological conditions. Elevated circDhx32 inhibited the transcriptional activation of AdipoR1 by binding to FOXO1. Conversel\n                    <jats:underline>y<\/jats:underline>\n                    , circDhx32 deficiency alleviated the inflammatory responses in I\/R-treated mice and H\/R-treated cardiomyocytes including decreased mRNA expression levels and release of inflammatory cytokines such as IL-6, TNF-\u03b1 and IL-1\u03b2 potentially through modulation of the AdipoR1-AMPK-NF-\u03baB signaling pathway. In conclusion, ALKBH5 acted as m\n                    <jats:sup>6<\/jats:sup>\n                    A eraser accompanied by the m\n                    <jats:sup>6<\/jats:sup>\n                    A readers YTHDF2 and YTHDC1 to promote high expression and nuclear retention of circDhx32 under pathological conditions. CircDhx32 regulated the inflammatory responses to cardiac I\/R injury by targeting the AdipoR1-AMPK-NF-\u03baB signaling pathway, which competed with AdipoR1 for FOXO1. These results revea\n                    <jats:underline>l<\/jats:underline>\n                    a novel mechanism underlying cardiac ischaemic injury, and circDhx32 is expected to be a potential therapeutic target for early intervention in ischaemic cardiac disease.\n                  <\/jats:p>","DOI":"10.1038\/s41401-025-01593-9","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T04:08:16Z","timestamp":1750133296000},"page":"2924-2937","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Circular RNA circDhx32 promotes cardiac inflammatory responses in mouse cardiac ischemia-reperfusion injury via binding to FOXO1 competed with AdipoR1"],"prefix":"10.1038","volume":"46","author":[{"given":"Wei","family":"Si","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-hua","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao-yue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-ting","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-tao","family":"Diao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-lun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-tao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-ying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-ting","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-ting","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng-fei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-feng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"1593_CR1","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.1161\/CIRCRESAHA.121.318992","volume":"130","author":"H Xiao","year":"2022","unstructured":"Xiao H, Zhang M, Wu H, Wu J, Hu X, Pei X, et al. 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