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As a sodium-glucose cotransporter 2 inhibitor, dapagliflozin (DAPA) has been demonstrated to be cardioprotective, in addition to its hypoglycemic effect. However, the precise mechanism of DAPA in myocardial hypertrophy remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>H9C2 rat cardiomyoblast cell line were subjected to isoproterenol (ISO)-induced hypertrophy and erastin-induced ferroptosis, and treated with DAPA, ferrostatin-1, KEAP1 activator K67, or inhibitor ML334. Hypertrophic markers and cell surface area were assessed by quantitative real-time polymerase chain reaction and rhodamine-phalloidin staining. Ferroptosis was evaluated by measuring glutathione (GSH), malondialdehyde, reactive oxygen species, lipid peroxidation, intracellular ferrous iron, and mitochondrial membrane potential. Protein expression of KEAP1, NRF2, solute carrier family 7 member 11, and GSH peroxidase 4 was determined by western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>DAPA attenuated ISO-induced cardiomyocyte hypertrophy and suppressed ferroptosis by inhibiting KEAP1 to activate NRF2, upregulating downstream targets. GSH peroxidase 4 knockdown abolished DAPA\u2019s protective effects. KEAP1 reactivation with K67 reversed DAPA-mediated cardioprotection, whereas KEAP1 inhibition with ML334 recapitulated it.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DAPA exerts a protective role in myocardial hypertrophy by inhibiting KEAP1\u2013NRF2-mediated ferroptosis pathway, providing novel insights into the potential mechanism and application of DAPA on cardiovascular diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag120","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:02:41Z","timestamp":1792670561000},"source":"Crossref","is-referenced-by-count":0,"title":["Dapagliflozin attenuates cardiomyocyte hypertrophy by inhibiting KEAP1\u2013NRF2-mediated ferroptosis pathway"],"prefix":"10.1093","volume":"78","author":[{"given":"Liying","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Guangzhou Eighth People\u2019s Hospital, Guangzhou Medical University , Guangzhou, Guangdong 510440 ,","place":["P.R. 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