Jürgen Bernhagen

Cardiovascular disease (CVD) remains the leading global cause of death, driven by complex mechanisms, in which chronic inflammation plays a central role. 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‐like 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‐molecule 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‐dopachrome tautomerase (D‐DT) 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.

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Ibudilast reduces PD-L1 expression in CD74+ from patient-derived organotypic cultures

Patient-derived organotypic cultures (PDOC) treated with Ibudilast

Ibudilast reduces brain metastasis in vivo without comprising the viability of cancer cells in vitro

Ibudilast reverts the protumorigenic signature of CD74+ microglia/macrophages in vivo

Gene set enrichment analysis of CD74+ microglia/macrophages

List of marker genes defining each CD45⁺ immune cell population identified by single-cell RNA-seq

List of flow cytometry antibodies