Macrophage migration inhibitory factor in atrial fibrillation
Xize Wu1, Shan Gao1, Ruiying Wang1
1Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Frontiers in Immunology
|July 17, 2026
Summary
Macrophage migration inhibitory factor (MIF) plays a dual role in atrial fibrillation (AF), contributing to both electrical and structural remodeling. Targeting MIF offers potential for AF biomarkers and therapies, but requires precise strategies to maintain its beneficial functions.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Macrophage migration inhibitory factor (MIF) is increasingly recognized for its significant role in the development and progression of atrial fibrillation (AF).
- MIF exhibits complex regulatory functions, acting as both a pro-inflammatory mediator and an antioxidant, influencing cardiac remodeling.
- Its involvement spans electrical and structural changes within the atria, making it a key factor in AF pathophysiology.
Purpose of the Study:
- To systematically review the multifaceted roles of MIF in atrial fibrillation.
- To explore MIF's potential as a diagnostic biomarker and a therapeutic target for AF.
- To discuss the mechanistic pathways through which MIF influences atrial remodeling and fibrosis.
Main Methods:
- Systematic review of existing literature on MIF and its association with atrial fibrillation.
- Analysis of mechanistic studies detailing MIF's effects on atrial electrical and structural remodeling.
- Evaluation of clinical data linking circulating MIF levels to AF characteristics and outcomes.
- Review of preclinical therapeutic strategies targeting MIF and its signaling pathways.
Main Results:
- MIF drives atrial electrical remodeling via pro-inflammatory cytokines, ion channel modulation, calcium disruption, and connexin 43 downregulation.
- MIF promotes atrial structural remodeling and fibrosis by activating fibroblasts and modulating the TGF-β/Smad pathway.
- Elevated circulating MIF levels are independently associated with AF severity, atrial fibrosis, and adverse cardiovascular outcomes.
- MIF's antioxidant properties, mediated by its TPOR activity, influence perioperative AF prediction.
- Preclinical studies show antiarrhythmic potential of MIF inhibition, but highlight risks of non-selective blockade.
Conclusions:
- MIF is a critical mediator in AF pathogenesis, affecting both electrical and structural remodeling.
- Circulating MIF levels serve as a valuable biomarker for AF burden and prognosis.
- Targeting MIF for AF therapy requires selective approaches to harness its benefits while mitigating potential harm.
- Further research is needed to develop precise therapeutic strategies and personalized treatment approaches for AF based on MIF.