Abstract 4141348: High-intensity Interval Training Improves Cardiac Function and Increases Expression of Genes Promoting Cardiomyocyte Proliferation in Myocardial-infarcted Mice

Background: Previous studies in exercise-based therapies for heart failure patients have demonstrated significant improvements in symptoms and overall quality of care. However, several questions regarding exercise intensity and training modalities are yet to be answered. Also, whether and how high-intensity training (HIIT) may improve cardiac function following acute myocardial infarction (MI) has not been examined. Research Question: HIIT improves cardiac function in mice undergoing myocardial infarction. Approach: Mice were familiarized with treadmill running for five days before MI (LAD ligation); then, mice resumed HIIT following MI (MI+HIIT group). Each session of HIIT intervention in mice includes treadmill running at 90%-100% of the maximal running speed and following 30s of passive recovery, 15 sessions per day, three days per week (one exercise day followed by one rest day) for six weeks. Cardiac function was measured via ultrasound and compared among the MI+HIIT, MI mice without HIIT (MI-only), mice underwent sham operation (Sham), mice underwent HIIT without MI (HIIT-only), and control mice underwent none of these intervention (CON) groups. Cardiac cell proliferation was quantified via EdU immunohistochemistry. Cardiac Bulk-RNA sequencing data was generated to identify signaling mechanisms potentially impacted by HIIT and analyzed via the Deseq2 package and pathway enrichment analysis. Result: MI+MIIT mice showed significantly higher ejection fraction, fraction shortening, and cardiomyocyte EdU signal compared to the MI-only group. Pathway enrichment analysis showed that signaling pathways known for regulating cardiac regeneration, including PI3k-Akt, MAPK, Hippo, and TGFb, were significantly enriched. Also, expressions of growth factors promoting cardiomyocyte proliferation, including POSTN, FSTL1, and FST, were increased in MI+MIIT hearts. Conclusion: HIIT improved cardiac function in mice after MI; also, HIIT may promote regulators of heart regeneration and cardiomyocyte proliferation.