Jake E Doiron, Mahmoud H Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D Gehred, Tatiana Gromova, Jingshu Chen, Ian H Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W H Wilson Tang, Kyle B LaPenna, Thomas E Sharp, Traci T Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J Shah, Josef Pfeilschifter, Karl-Friedrich Beck, Thomas M Vondriska, Zhen Li, David J Lefer
{"title":"硫化氢缺乏和心脏代谢性HFpEF的治疗靶向：GLP-1/胰高血糖素激动剂协同效应的证据。","authors":"Jake E Doiron, Mahmoud H Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D Gehred, Tatiana Gromova, Jingshu Chen, Ian H Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W H Wilson Tang, Kyle B LaPenna, Thomas E Sharp, Traci T Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J Shah, Josef Pfeilschifter, Karl-Friedrich Beck, Thomas M Vondriska, Zhen Li, David J Lefer","doi":"10.1016/j.jacbts.2025.04.011","DOIUrl":null,"url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) presents significant treatment challenges. We assessed hydrogen sulfide (H<sub>2</sub>S) bioavailability in HFpEF patients and 2 animal models: the \"2-hit\" L-NAME + high-fat diet mouse model and ZSF1 obese rats. H<sub>2</sub>S 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 H<sub>2</sub>S donor improved diastolic function and reduced cardiac fibrosis. H<sub>2</sub>S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H<sub>2</sub>S bioavailability may provide a novel therapeutic strategy for HFpEF.</p>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":" ","pages":"101297"},"PeriodicalIF":8.4000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With GLP-1/Glucagon Agonism.\",\"authors\":\"Jake E Doiron, Mahmoud H Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D Gehred, Tatiana Gromova, Jingshu Chen, Ian H Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W H Wilson Tang, Kyle B LaPenna, Thomas E Sharp, Traci T Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J Shah, Josef Pfeilschifter, Karl-Friedrich Beck, Thomas M Vondriska, Zhen Li, David J Lefer\",\"doi\":\"10.1016/j.jacbts.2025.04.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Heart failure with preserved ejection fraction (HFpEF) presents significant treatment challenges. We assessed hydrogen sulfide (H<sub>2</sub>S) bioavailability in HFpEF patients and 2 animal models: the \\\"2-hit\\\" L-NAME + high-fat diet mouse model and ZSF1 obese rats. H<sub>2</sub>S 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 H<sub>2</sub>S donor improved diastolic function and reduced cardiac fibrosis. H<sub>2</sub>S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H<sub>2</sub>S bioavailability may provide a novel therapeutic strategy for HFpEF.</p>\",\"PeriodicalId\":14831,\"journal\":{\"name\":\"JACC: Basic to Translational Science\",\"volume\":\" \",\"pages\":\"101297\"},\"PeriodicalIF\":8.4000,\"publicationDate\":\"2025-06-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JACC: Basic to Translational Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jacbts.2025.04.011\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC: Basic to Translational Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jacbts.2025.04.011","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Hydrogen Sulfide Deficiency and Therapeutic Targeting in Cardiometabolic HFpEF: Evidence for Synergistic Benefit With GLP-1/Glucagon Agonism.
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.
期刊介绍：
JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.
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