Document Type
Article
Publication Date
8-6-2025
Publication Title
JACC Basic to Translational Science
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.
PubMed ID
40772898
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Doiron, Jake E.; Elbatreek, Mahmoud H.; Xia, Huijing; Yu, Xiaoman; Gehred, Natalie D.; Gromova, Tatiana; Chen, Jingshu; Driver, Ian H.; Muraoka, Naoto; Jensen, Martin; Shambhu, Smitha; Tang, W. H.Wilson; LaPenna, Kyle B.; Sharp, Thomas E.; Goodchild, Traci T.; Xian, Ming; Xu, Shi; Quiriarte, Heather; Allerton, Timothy D.; Zagouras, Alexia; Wilcox, Jennifer; Shah, Sanjiv J.; Pfeilschifter, Josef; Beck, Karl Friedrich; Vondriska, Thomas M.; Li, Zhen; and Lefer, David J., "Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With GLP-1/Glucagon Agonism" (2025). School of Graduate Studies Faculty Publications. 389.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/389
10.1016/j.jacbts.2025.04.011
Included in
Cardiovascular Diseases Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Medical Pharmacology Commons, Translational Medical Research Commons