Additionally, previous studies have shown that MIF is an upstream regulator of AMPK and cardioprotection (51, 52); sustained exogenous administration of recombinant MIF efficiently activates AMPK phosphorylation and prevents hearts from ischemic injury (37, 53); MIF-engineered mesenchymal stem cells derived exosomes significantly activated the AKT signaling pathway, one of AMPK downstream pathways, and ameliorated cardiomyocyte apoptosis and cardiac dysfunction in rats with myocardial infarction (54). This evidence concerns the gene MIF and myocardial infarction.