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.