Minutes that matter: time-efficient high-intensity interval training improves cardiac function with transcriptomic evidence in post-myocardial infarction mice.

High-intensity interval training (HIIT) improves cardiovascular performance, but the mechanisms remain incompletely delineated. We investigated whether HIIT improves left-ventricular (LV) remodeling after myocardial infarction (MI) in adult mice. Animals underwent permanent coronary ligation or sham surgery and were randomized to Control, HIIT-only, Sham, MI-only, and MI + HIIT. HIIT comprised 15 treadmill bouts (60 s at 90%-110% maximal running speed followed by 30 s rest), 3 days/week for 6 weeks. Baseline echocardiography 1 week after MI confirmed comparable LV dysfunction in MI-only and MI + HIIT groups. After intervention, the MI + HIIT group showed higher running capacity, improved LV ejection fraction (26.18% vs. 16.19%; p < 0.01) and fractional shortening (12.24% vs. 7.41%; p < 0.01), and less LV dilation versus MI-only. Myocardial fibrosis was reduced in MI + HIIT (8.85% vs. 13.17%; p < 0.01), consistent with physiological remodeling. 5-ethynyl-2'-deoxyuridine (EdU) incorporation identified more DNA synthesis in MI + HIIT (1.71%) and HIIT-only (1.24%) hearts. Bulk RNA sequencing showed coordinated upregulation of contractile and metabolic pathways and downregulation of apoptosis and inflammatory signaling, aligning with improved cell-cycle activity and oxidative-metabolic efficiency. Collectively, HIIT enhanced exercise capacity and cardiac function, attenuated fibrosis, and reprogrammed cardiac gene expression toward pro-contractile and anti-inflammatory programs consistent with a cell-cycle-permissive state in a post-MI mouse model.