A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation.

ABSTRACT: Macrophage migration inhibitory factor (MIF) is an innate cytokine that regulates both inflammatory and homeostatic responses. MIF is expressed by cardiomyocytes, where it exerts a protective action against ischemia-reperfusion (I/R) injury by activating AMP-activated protein kinase (AMPK). This effect is attenuated in the senescent heart due to an intrinsic, age-related reduction in MIF expression. We hypothesized that treating the aged heart with the small molecule MIF agonist (MIF20) can reinforce protective MIF signaling in cardiomyocytes, leading to a beneficial effect against I/R stress. The administration of MIF20 at the onset of reperfusion was found to not only decrease myocardial infarct size but also preserves systolic function in the aged heart. Protection from I/R injury was r

SUBMITTER: Wang H 

PROVIDER: S-EPMC10932879 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature