Authors

Jake E. Doiron, LSU Health Sciences Center - New OrleansFollow
Mahmoud H. Elbatreek, Cedars-Sinai Medical Center, Los Angeles, CA
Huijing Xia, LSU Health Sciences Center - New OrleansFollow
Xiaoman Yu, Cedars-Sinai Medical Center, Los Angeles, CA
Natalie D. Gehred, David Geffen School of Medicine at UCLA
Tatiana Gromova, David Geffen School of Medicine at UCLA
Jingshu Chen, Gordian Biotechnology, South San Francisco, CA
Ian H. Driver, Gordian Biotechnology, South San Francisco, CA
Naoto Muraoka, Gordian Biotechnology, South San Francisco, CA
Martin Jensen, Gordian Biotechnology, South San Francisco, CA
Smitha Shambhu, Gordian Biotechnology, South San Francisco, CA
W. H.Wilson Tang, Cleveland Clinic, Cleveland, OH
Kyle B. LaPenna, LSU Health Sciences Center - New OrleansFollow
Thomas E. Sharp, University of South Florida, Tampa
Traci T. Goodchild, Cedars-Sinai Medical Center, Los Angeles, CA
Ming Xian, Brown University, Providence, RI
Shi Xu, Brown University, Providence, RI
Heather Quiriarte, Pennington Biomedical Research Center, Baton Rouge, LA
Timothy D. Allerton, Pennington Biomedical Research Center, Baton Rouge, LA
Alexia Zagouras, Cleveland Clinic Foundation, Cleveland, OH
Jennifer Wilcox, Cleveland Clinic Foundation, Cleveland, OH
Sanjiv J. Shah, Northwestern University Medicine, Chicago, IL
Josef Pfeilschifter, Goethe University, Frankfurt am Main, Germany
Karl Friedrich Beck, Goethe University, Frankfurt am Main, Germany
Thomas M. Vondriska, David Geffen School of Medicine at UCLA
Zhen Li, Cedars-Sinai Medical Center, Los Angeles, CA
David J. Lefer, Cedars-Sinai Medical Center, Los Angeles, CA

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

Share

COinS