Distinct roles of MIF in the pathogenesis of ischemic heart disease

The role of macrophage migration inhibitory factor (MIF) as a multifunctional cytokine in immunomodulation and inflammatory response is increasingly appreciated. Ischemic heart disease (IHD), the leading cause of global mortality, remains a focal point of research owing to its intricate pathophysiology. MIF has been identified as a critical player in IHD, where it exerts distinct roles. On one hand, MIF plays a protective role by enhancing energy metabolism through activation of AMPK, resisting oxidative stress, inhibiting activation of the JNK pathway, and maintaining intracellular calcium ion homeostasis. Additionally, MIF exerts protective effects through mesenchymal stem cells and exosomes. On the other hand, MIF can assume a pro-inflammatory role, which contributes to the exacerbation of IHD's development and progression. Furthermore, MIF levels significantly increase in IHD patients, and its genetic polymorphisms are positively correlated with prevalence and severity. These findings position MIF as a potential biomarker and therapeutic target in the management of IHD. This review summarizes the structure, source, signaling pathways and biological functions of MIF and focuses on its roles and clinical characteristics in IHD. The genetic variants of MIF associated with IHD is also discussed, providing more understandings of its complex interplay in the disease's pathology.