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Inflammatory pathways contribute to all stages of CVD, from endothelial dysfunction and plaque formation to erosion, rupture and myocardial injury. Among the mediators implicated, macrophage migration inhibitory factor (MIF) has emerged as a pivotal player. MIF is a unique cytokine with chemokine\u2010like activity that promotes leukocyte recruitment, amplifies inflammatory cascades and modulates vascular function. Elevated circulating and tissue MIF levels correlate with disease severity, plaque instability and adverse outcomes in coronary artery disease and acute coronary syndrome, positioning MIF as both a biomarker and a therapeutic target. Preclinical studies demonstrate that MIF blockade, via small\u2010molecule inhibitors, engineered peptides or monoclonal antibodies, attenuates vascular inflammation and stabilizes plaques. However, clinical development for cardiovascular indications remains limited, with current trials focused on oncology and neuroinflammation. This review synthesizes current knowledge on MIF and its homologue D\u2010dopachrome tautomerase (D\u2010DT) in CVD, explores diagnostic and therapeutic potential and highlights emerging concepts such as sex differences. Understanding this axis could inform the development of novel immunocardiovascular therapies and personalized treatment strategies.<\/jats:p>","DOI":"10.1111\/bph.70584","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:37:23Z","timestamp":1784335043000},"page":"5732-5751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of macrophage migration inhibitory factor (MIF) in the pathogenesis and progression of cardiovascular disease"],"prefix":"10.1111","volume":"183","author":[{"given":"Shreya","family":"Mahabhashyam","sequence":"first","affiliation":[{"name":"Cardiovascular Disease Program, Biomedicine Discovery Institute Monash University  Melbourne Victoria Australia"},{"name":"Department of Physiology Monash University  Melbourne Victoria 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