High-intensity interval training attenuates cardiac injury by targeting ferroptosis and endoplasmic reticulum-stress in male rats with heart failure.

This study investigated the effects of high-intensity interval training (HIIT) on endoplasmic reticulum (ER) stress, ferroptosis, and iron deposition in rats with heart failure (HF). HF was induced by intraperitoneal injection of isoprenaline (130 mg/kg/day) for 4 days. Afterward, rats were divided into control healthy (Control), HF sedentary (HF-Sed), and HF HIIT (HF-HIT) groups. The HF-HIT group underwent HIIT (5 intervals of 4 min at 85%-90% VO(2max), separated by 2 min at 50%-60% VO(2max)) for 8 weeks. Biomarkers of ER stress, ferroptosis, and oxidative stress, along with cardiac function, were measured post-intervention. HIIT reduced cardiac fibrosis and iron deposition while increasing cystine/glutamate transporter (SLC7A11), glutathione peroxidase 4 (GPX4), and SOD levels. Additionally, protein levels of glucose-regulated protein 78 (GRP78), protein kinase RNA-activated-like ER kinase (PERK), and activating transcription factor 4 (ATF4) decreased after HIIT. These findings suggest that HIIT alleviates ferroptosis and ER stress via the PERK/ATF4/SLC7A11/GPX4 pathway, offering protective effects against HF.