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Updated: Sep 20, 2026

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction
Published on: March 29, 2024
Dapagliflozin Prevents Heart Failure With Preserved Ejection Fraction by Inhibiting the Sodium/Hydrogen Exchanger
Man Liu1, Hong Liu1, Eunji Kim1
1Cardiovascular Division, Department of Medicine, The Lillehei Heart Institute, University of Minnesota at Twin Cities, Minneapolis, Minnesota, USA.
Abstract:
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.
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