Canagliflozin Regulates Ferroptosis, Potentially via Activating AMPK/PGC-1α/Nrf2 Signaling in HFpEF Rats

Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to ameliorate major adverse cardiovascular events in patients with heart failure preserved ejection fraction (HFpEF), but the exact mechanism is unknown. Ferroptosis a form of programmed necrosis. Herein, we verified that canagliflozin (CANA) ameliorates function HFpEF rats, partly by regulating ferroptosis, which may be activated AMPK/PGC-1α/Nrf2 signaling. Methods: An model was established and subjected CANA treatment. Blood pressure monitored, echocardiography performed at 12 th week. Pathological examination performed, expression ferroptosis-associated proteins signaling related detected. Results: had an antihypertensive effect increased E/A ratios rats. Myocardial pathology ameliorated, on basis decreased cross-sectional area intercellular fibrosis. Acyl-CoA synthetase long-chain family member 4 (ACSL4) increased, whereas ferritin heavy chain 1 (FTH1) showed iron overload. reversed changes ACSL4 FTH1, accumulation, did not alter glutathione peroxidase (GPX4) expression. The heme oxygenase (HO-1) group reverted after Conclusions: regulates potentially via activating