The role of macrophage migration inhibitory factor (MIF) in the pathogenesis and progression of cardiovascular
Shreya Mahabhashyam1,2, James Harris3,4, Jürgen Bernhagen5,6
1Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.
Insights
Chronic inflammation drives cardiovascular disease (CVD). Macrophage migration inhibitory factor (MIF) is a key mediator, showing potential as a biomarker and therapeutic target for novel immunocardiovascular therapies.
Area of Science:
- Immunology
- Cardiology
- Biochemistry
Background:
- Cardiovascular disease (CVD) is a leading cause of death globally.
- Chronic inflammation is central to CVD pathogenesis, affecting all stages from endothelial dysfunction to myocardial injury.
- Macrophage migration inhibitory factor (MIF) is identified as a pivotal cytokine mediator in CVD.
Purpose of the Study:
- To review current knowledge on MIF and its homologue D-dopachrome tautomerase (D-DT) in CVD.
- To explore the diagnostic and therapeutic potential of the MIF/D-DT axis in cardiovascular medicine.
- To highlight emerging concepts, such as sex differences, in MIF's role in CVD.
Main Methods:
- Literature review synthesizing current research on MIF and D-DT in cardiovascular disease.
- Analysis of preclinical studies investigating MIF blockade strategies (small molecules, peptides, antibodies).
- Examination of clinical trial data, noting current focus on oncology and neuroinflammation.
Main Results:
- Elevated MIF levels correlate with CVD severity, plaque instability, and adverse outcomes in coronary artery disease and acute coronary syndrome.
- Preclinical studies show MIF blockade attenuates vascular inflammation and stabilizes plaques.
- Clinical development of MIF-targeted therapies for CVD is limited but holds promise.
Conclusions:
- The MIF/D-DT axis represents a significant target for novel immunocardiovascular therapies.
- Understanding MIF's role, including sex-specific effects, can inform personalized treatment strategies for CVD.
- Further research and clinical trials are needed to translate MIF-targeted therapies into cardiovascular practice.
Abstract:
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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