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During HT, infiltrating neutrophils are influenced and regulated by various other cell types, contributing to myocardial IR injury through the excessive release of neutrophil extracellular traps (NETs). Nonetheless, the precise mechanisms underlying the interactions between neutrophils and other non\u2010cardiomyocytes remain largely unexplored. Single\u2010cell RNA sequencing is employed to characterize the cellular landscape and to explore the crosstalk between neutrophils and other non\u2010cardiomyocytes. The role of AT\u2010rich interactive domain\u2010containing protein 3A (ARID3A) during HT is further examined using myeloid\u2010specific ARID3A\u2010knockout mice. Molecular docking analyses are conducted to identify the target of 4\u2010octyl itaconate (4\u2010OI). These results reveal that M1 macrophages recruited during the reperfusion of HT promote NETs formation and myocardial IR injury through THBS1\/CD47 axis, whereas CD47 induces NETosis by activating the p38 MAPK signaling. Exogenous administration of 4\u2010OI specifically inhibits ARID3A in macrophages, thereby suppressing NETosis and alleviating myocardial IR injury. These findings indicate that THBS1\/CD47 signaling is a critical bridge mediating the interaction between M1 macrophages and NETs\u2010associated neutrophils, and identify 4\u2010OI as a promising therapeutic candidate for the treatment of myocardial IR injury following HT.<\/jats:p>","DOI":"10.1002\/advs.202509952","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T11:19:19Z","timestamp":1757157559000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of Macrophage ARID3A Alleviates Myocardial Ischemia\u2010Reperfusion Injury After Heart Transplantation by Reducing THBS1\/CD47 Signaling\u2010Mediated Neutrophil Extracellular Traps Formation"],"prefix":"10.1002","volume":"12","author":[{"given":"Hao","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan Hubei 430060 P. R. 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