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Enhanced efferocytosis by cardiac resident macrophages (RMs) has therapeutic potential for inflammation resolution. The unsaturated long-chain fatty acid Maresin1 (MaR1) exhibits potent anti-inflammatory properties that is devoid of immunosuppressive effects. However, its therapeutic potential in myocardial I\/R injury and regulatory mechanisms in cardiac RMs remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A clinical case\u2012control study was conducted and revealed a negative association between circulating MaR1 levels and inflammatory markers and the severity of I\/R injury in patients with ST-elevation myocardial infarction. Mice treated with MaR1 after myocardial I\/R injury showed improvements in cardiac function and efferocytosis by cardiac RMs. Genetic ablation of cardiac RMs abolished MaR1-mediated cardioprotection. To explore the mechanism underlying this protection, we performed transcriptomic, metabolomics, and lipidomic analyses and identified fatty acid \u03b2-oxidation potentiation as a key metabolic signature in MaR1-treated RMs. Moreover, MaR1 directly bound peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3), inducing the transcriptional activation of its downstream efferocytosis-related target CD204. Specific knockout of PPAR\u03b3 in RMs significantly attenuated MaR1-enhanced efferocytosis. Notably, oral supplementation with the MaR1 precursor docosahexaenoic acid (DHA) recapitulated these cardioprotective effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings prove that MaR1 plays a protective role in myocardial I\/R injury by facilitating efferocytosis by RMs and the resolution of inflammation. These results offer novel therapeutic perspectives for the management of myocardial I\/R injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag017","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:53:13Z","timestamp":1768481593000},"page":"397-411","source":"Crossref","is-referenced-by-count":6,"title":["Maresin 1 ameliorates myocardial ischaemia\u2012reperfusion injury by promoting tissue resident macrophage efferocytosis"],"prefix":"10.1093","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-5159","authenticated-orcid":false,"given":"Xuan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Cardiology, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing Key Laboratory for Cardiovascular Information and Health Engineering Medicine , No. 321 Zhongshan Road, Nanjing 210008 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