Macrophage Migration Inhibitory Factor (MIF) drives cardiovascular disease, a promising therapeutic target.

Cardiovascular disease (CVD) remains the leading global cause of death, with chronic inflammation playing a central role in its complex pathogenesis. Inflammatory pathways contribute to all stages of CVD, from endothelial dysfunction and plaque formation to rupture and myocardial injury. Macrophage migration inhibitory factor (MIF) has emerged as a pivotal mediator, promoting leukocyte recruitment, amplifying inflammatory cascades, and modulating vascular function. Elevated MIF levels correlate with disease severity and adverse outcomes, positioning it as both a biomarker and a potential therapeutic target.

This comprehensive review synthesizes current knowledge on macrophage migration inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (D-DT) in the pathogenesis and progression of cardiovascular disease (CVD). The authors explored the diagnostic and therapeutic potential of targeting the MIF axis, highlighting emerging concepts such as sex differences in its role. The review systematically compiled findings from preclinical studies and clinical observations, focusing on MIF's multifaceted involvement in inflammation, vascular function, and plaque dynamics to inform future immunocardiovascular therapies.

MIF, a unique cytokine with chemokine-like activity, actively promotes leukocyte recruitment, amplifies inflammatory cascades, and modulates vascular function in CVD. Elevated circulating and tissue MIF levels consistently correlate with disease severity, plaque instability, and adverse outcomes in coronary artery disease and acute coronary syndrome. This positions MIF as a critical biomarker for CVD progression. Preclinical studies have repeatedly demonstrated that MIF blockade, achieved through small-molecule inhibitors, engineered peptides, or monoclonal antibodies, effectively attenuates vascular inflammation and stabilizes atherosclerotic plaques. The review also highlights the significant, yet less understood, role of D-DT and underscores the importance of considering sex differences in MIF's impact on CVD pathogenesis. > Preclinical studies consistently demonstrate that MIF blockade, via small-molecule inhibitors, engineered peptides or monoclonal antibodies, attenuates vascular inflammation and stabilizes plaques.