Aerobic exercise inhibits GSDME-dependent myocardial cell pyroptosis to protect ischemia-reperfusion injury.

Background: Acute myocardial infarction (AMI) remains a significant cause of global mortality, exacerbated by ischemia-reperfusion (IR) injury. Myocardial cell pyroptosis has emerged as a critical pathway influencing IR injury severity.

Methods: We aimed to investigate the cardioprotective effects of aerobic exercise on IR injury by examining the modulation of IGFBP2 and its impact on GSDME-dependent myocardial cell pyroptosis. Mechanistic pathways were explored using western blot analysis, ELISA, immunofluorescence, and echocardiography.

Results: Our findings demonstrate that aerobic exercise leads to increased circulating levels of IGFBP2, which effectively suppresses GSDME-dependent myocardial cell pyroptosis. This regulation occurs via the AKT-GSK3β signaling pathway, involving VDAC1 phosphorylation, thereby enhancing mitochondrial function and reducing oxidative stress.

Conclusion: In conclusion, our study highlights the role of IGFBP2 in mitigating GSDME-dependent pyroptosis as a mechanism through which aerobic exercise exerts cardioprotective effects against IR injury. These insights suggest potential therapeutic targets for managing acute myocardial infarction.