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Updated: Sep 12, 2025

Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With
Jake E Doiron1, Mahmoud H Elbatreek2, Huijing Xia1
1Department of Pharmacology and Cardiovascular Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Abstract:
Heart failure with preserved ejection fraction (HFpEF) presents significant treatment challenges. We assessed hydrogen sulfide (H2S) bioavailability in HFpEF patients and 2 animal models: the "2-hit" L-NAME + high-fat diet mouse model and ZSF1 obese rats. H2S levels were significantly reduced in patients and both models, linked to decreased cystathionine-γ-lyase expression and increased sulfide quinone oxidoreductase. Cystathionine-γ-lyase knockout worsened HFpEF, whereas pharmacological supplementation with an H2S donor improved diastolic function and reduced cardiac fibrosis. H2S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H2S bioavailability may provide a novel therapeutic strategy for HFpEF.
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