Dapagliflozin Prevents Heart Failure With Preserved Ejection Fraction by Inhibiting the Sodium/Hydrogen Exchanger
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown protective effects against heart failure with preserved ejection fraction (HFpEF), but SGLT2 is not expressed significantly in the heart. Here, we investigated the mechanism by which the SGLT2 inhibitor dapagliflozin (Dapa) alters HypoMg-associated HFpEF. HypoMg was induced by a low-Mg diet in mice or in a human cardiomyocyte cell line. Three weeks of Dapa treatment prevented HypoMg-induced HFpEF in mice. In RL-14 cardiomyocytes, sodium-hydrogen exchanger 1 (NHE1) overexpression or activation mimicked the cellular effects of HypoMg. Dapa reversed these changes. Dapa prevented cardiac HFpEF by inhibiting cardiomyocyte NHE1 activity and suppressing macrophage activation.
Authors
- Samuel C. Dudley (ORCID: https://orcid.org/0000-0001-5843-5961)
- Mitchell C. Neumann
- Man Liu (ORCID: https://orcid.org/0000-0002-7878-7697)
- Eunji Kim (ORCID: https://orcid.org/0000-0002-1908-5310)
- Gyeoung-Jin Kang
- Hong Liu
- Ruthvika Murikinati
- Madeline Johnson
Institutions
- University of Minnesota (US)
- Twin Cities Orthopedics (US)
- Minneapolis Heart Institute Foundation (US)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2026-09-18
- DOI
- https://doi.org/10.1016/j.jacbts.2026.101698
- Primary Topic
- Diabetes Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health