Empagliflozin Attenuates Ferroptosis in Acute Myocardial Infarction via the AMPK/NRF2/SLC7A11 Signaling Pathway.
X, T., X, Z., & C, L. (2026). Empagliflozin Attenuates Ferroptosis in Acute Myocardial Infarction via the AMPK/NRF2/SLC7A11 Signaling Pathway.. International heart journal. https://doi.org/10.1536/ihj.25-386
X T, X Z, C L. Empagliflozin Attenuates Ferroptosis in Acute Myocardial Infarction via the AMPK/NRF2/SLC7A11 Signaling Pathway.. International heart journal. 2026; doi: 10.1536/ihj.25-386
X T, X Z, C L. Empagliflozin Attenuates Ferroptosis in Acute Myocardial Infarction via the AMPK/NRF2/SLC7A11 Signaling Pathway.[J]. International heart journal. 2026. DOI: 10.1536/ihj.25-386.
@article{x2026,
author = {Tang X and Zhao X and Liu C},
title = {Empagliflozin Attenuates Ferroptosis in Acute Myocardial Infarction via the AMPK/NRF2/SLC7A11 Signaling Pathway.},
journal = {International heart journal},
year = {2026},
doi = {10.1536/ihj.25-386},
note = {PMID: 42543668},
}
TY - JOUR AU - Tang X AU - Zhao X AU - Liu C TI - Empagliflozin Attenuates Ferroptosis in Acute Myocardial Infarction via the AMPK/NRF2/SLC7A11 Signaling Pathway. T2 - International heart journal PY - 2026 DO - 10.1536/ihj.25-386 AN - PMID:42543668 ER -
Emerging evidence implicates ferroptosis in myocardial ischemic injury. This study aimed to investigate whether empagliflozin (EMP) suppresses ferroptosis in acute myocardial infarction (AMI) via the AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (NRF2)/solute carrier family 7 member 11 (SLC7A11) pathway.Hypoxia/reoxygenation (H/R)-injured HL-1 cardiomyocytes were treated with EMP (10, 20, 30 μM). Cell viability, morphology, damage, and apoptosis were assessed by CCK-8, inverted microscopy, lactate dehydrogenase (LDH) release, and flow cytometry. H/R-injured cells were treated with 30 μM EMP and/or ferrostatin-1 (Fer-1), followed by measurements of Fe2+, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), superoxide dismutase (SOD), lipid ROS (C11-BODIPY), ferroptosis-related proteins [SLC7A11, glutathione peroxidase 4 (GPX4), phospho-AMPK (p-AMPK), AMPK, NRF2 using Western blot], and NRF2 nuclear translocation (using immunofluorescence). An AMI mouse model was established. Myocardial pathology and infarct size were evaluated, and AMPK/NRF2/SLC7A11 pathway proteins and myocardial Fe2+/MDA/GSH levels were measured.EMP partially reversed H/R-induced cardiomyocyte shrinkage and membrane rupture, reduced viability, elevated LDH, and increased apoptosis. Among cell death inhibitors, Fer-1 exerted maximal protection, indicating ferroptosis may be the predominant death type in H/R-injured HL-1 cardiomyocytes. EMP mirrored the anti-ferroptotic activity of Fer-1. Mechanistically, EMP decreased cytoplasmic NRF2 and the p-AMPK/AMPK ratio while promoting the translocation of NRF2 from the cytoplasm to the nucleus. EMP activated the AMPK/NRF2/SLC7A11 axis to attenuate ferroptosis in AMI mice.In conclusion, EMP suppressed ferroptosis and ameliorated cellular injury in H/R-injured cardiomyocytes by activating the AMPK/NRF2/SLC7A11 pathway, with efficacy confirmed in vivo during AMI.