{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T07:15:33Z","timestamp":1794035733048,"version":"4.8.0"},"reference-count":145,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Department of Science and Technology of Liaoning Province","doi-asserted-by":"publisher","award":["2022JH2\/101300086, Liaoning Young Elite Scientists Sponsorship Program, YXMJ-MZY-02"],"award-info":[{"award-number":["2022JH2\/101300086, Liaoning Young Elite Scientists Sponsorship Program, YXMJ-MZY-02"]}],"id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008844","name":"Liaoning University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["Youth Innovation Team"],"award-info":[{"award-number":["Youth Innovation Team"]}],"id":[{"id":"10.13039\/501100008844","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Macrophage migration inhibitory factor (MIF) is a multifunctional upstream cytokine that has attracted increasing attention for its role in the initiation and perpetuation of atrial fibrillation (AF). This review systematically discusses the dual regulatory roles of MIF in AF and its potential as both a biomarker and a therapeutic target. Mechanistically, MIF drives atrial electrical remodeling by promoting the release of pro-inflammatory cytokines, modulating ion channels, disrupting calcium homeostasis, and downregulating connexin 43. Concurrently, MIF promotes atrial structural remodeling and fibrosis through the activation of fibroblasts, enhancement of collagen deposition, and modulation of the TGF-\u03b2\/Smad signaling pathway. Clinical studies have demonstrated that circulating MIF levels are independently associated with AF type, disease burden, the extent of atrial fibrosis, and long-term adverse outcomes, including heart failure, stroke, and myocardial infarction. MIF possesses an N-terminal tautomerase activity and a thiol-protein oxidoreductase (TPOR) activity mediated by its Cys57-Ala-Leu-Cys60 (CALC) motif, the latter serving as the structural basis for its antioxidant functions. Reflecting this property, the dynamic perioperative changes in MIF exhibit a biphasic predictive value for postoperative AF (POAF). Therapeutically, direct MIF inhibition (e.g., with 4-IPP) or blockade of downstream signaling (e.g., with CXCR2 antagonists) has shown antiarrhythmic potential in animal models; however, non-selective pan-inhibition may inadvertently ablate the endogenous antioxidant and cardioprotective signals of MIF. Future research should focus on elucidating the molecular switch that governs the functional transition of MIF, developing highly selective drugs targeting the disease-related conformational isoform oxMIF to precisely block pathogenic signaling, validating the existence of a MIF-TGF-\u03b2 positive feedback loop in atrial fibroblasts, implementing time-window-based intervention strategies, and incorporating MIF promoter polymorphisms into personalized patient stratification. Addressing these priorities will be essential to advance the clinical translation of MIF-targeted therapies for atrial fibrillation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1874330","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:48:15Z","timestamp":1782996495000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage migration inhibitory factor in atrial fibrillation"],"prefix":"10.3389","volume":"17","author":[{"given":"Xize","family":"Wu","sequence":"first","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Gao","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, 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