Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress
Atrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (H2S) is a gaseous signalling molecule with ca...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.690371/full |
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| author | Heng-Jing Hu Heng-Jing Hu Xiu-Heng Wang Yao Liu Tian-Qing Zhang Zheng-Rong Chen Chi Zhang Zhi-Han Tang Shun-Lin Qu Hui-Fang Tang Zhi-Sheng Jiang Zhi-Sheng Jiang Zhi-Sheng Jiang |
| author_facet | Heng-Jing Hu Heng-Jing Hu Xiu-Heng Wang Yao Liu Tian-Qing Zhang Zheng-Rong Chen Chi Zhang Zhi-Han Tang Shun-Lin Qu Hui-Fang Tang Zhi-Sheng Jiang Zhi-Sheng Jiang Zhi-Sheng Jiang |
| author_sort | Heng-Jing Hu |
| collection | DOAJ |
| description | Atrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (H2S) is a gaseous signalling molecule with cardioprotective, anti-myocardial fibrosis and improved energy metabolism effects. Nevertheless, the specific mechanism by which H2S improves the progression of atrial fibrosis to AF remains unclear. A case-control study of patients with and without AF was designed to assess changes in H2S, the Warburg effect, and ERS in AF. The results showed that AF can significantly reduce cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate thiotransferase (3-MST) expression and the H2S level, induce cystathionine-β-synthase (CBS) expression; increase the Warburg effect, ERS and atrial fibrosis; and promote left atrial dysfunction. In addition, AngII-treated SD rats had an increased Warburg effect and ERS levels and enhanced atrial fibrosis progression to AF compared to wild-type SD rats, and these conditions were reversed by sodium hydrosulfide (NaHS), dichloroacetic acid (DCA) or 4-phenylbutyric acid (4-PBA) supplementation. Finally, low CSE levels in AngII-induced HL-1 cells were concentration- and time-dependent and associated with mitochondrial dysfunction, apoptosis, the Warburg effect and ERS, and these effects were reversed by NaHS, DCA or 4-PBA supplementation. Our research indicates that H2S can regulate the AngII-induced Warburg effect and ERS and might be a potential therapeutic drug to inhibit atrial fibrosis progression to AF. |
| first_indexed | 2024-12-19T02:31:31Z |
| format | Article |
| id | doaj.art-500f641513f7455f9fdf58329036b9c7 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T02:31:31Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-500f641513f7455f9fdf58329036b9c72022-12-21T20:39:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-12-011210.3389/fphar.2021.690371690371Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum StressHeng-Jing Hu0Heng-Jing Hu1Xiu-Heng Wang2Yao Liu3Tian-Qing Zhang4Zheng-Rong Chen5Chi Zhang6Zhi-Han Tang7Shun-Lin Qu8Hui-Fang Tang9Zhi-Sheng Jiang10Zhi-Sheng Jiang11Zhi-Sheng Jiang12Department of Cardiology Laboratory, First Affiliated Hospital of University of South China, Hengyang, ChinaPostdoctoral Research Station of Basic Medicine, University of South China, Hengyang, ChinaDepartment of Nuclear Medicine Lab, First Affiliated Hospital of University of South China, Hengyang, ChinaDepartment of Cardiology Laboratory, First Affiliated Hospital of University of South China, Hengyang, ChinaDepartment of Cardiology Laboratory, First Affiliated Hospital of University of South China, Hengyang, ChinaDepartment of Cardiology Laboratory, First Affiliated Hospital of University of South China, Hengyang, ChinaInstitute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, ChinaInstitute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, ChinaInstitute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, ChinaDepartment of Cardiology Laboratory, First Affiliated Hospital of University of South China, Hengyang, ChinaDepartment of Cardiology Laboratory, First Affiliated Hospital of University of South China, Hengyang, ChinaPostdoctoral Research Station of Basic Medicine, University of South China, Hengyang, ChinaInstitute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, ChinaAtrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (H2S) is a gaseous signalling molecule with cardioprotective, anti-myocardial fibrosis and improved energy metabolism effects. Nevertheless, the specific mechanism by which H2S improves the progression of atrial fibrosis to AF remains unclear. A case-control study of patients with and without AF was designed to assess changes in H2S, the Warburg effect, and ERS in AF. The results showed that AF can significantly reduce cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate thiotransferase (3-MST) expression and the H2S level, induce cystathionine-β-synthase (CBS) expression; increase the Warburg effect, ERS and atrial fibrosis; and promote left atrial dysfunction. In addition, AngII-treated SD rats had an increased Warburg effect and ERS levels and enhanced atrial fibrosis progression to AF compared to wild-type SD rats, and these conditions were reversed by sodium hydrosulfide (NaHS), dichloroacetic acid (DCA) or 4-phenylbutyric acid (4-PBA) supplementation. Finally, low CSE levels in AngII-induced HL-1 cells were concentration- and time-dependent and associated with mitochondrial dysfunction, apoptosis, the Warburg effect and ERS, and these effects were reversed by NaHS, DCA or 4-PBA supplementation. Our research indicates that H2S can regulate the AngII-induced Warburg effect and ERS and might be a potential therapeutic drug to inhibit atrial fibrosis progression to AF.https://www.frontiersin.org/articles/10.3389/fphar.2021.690371/fullatrial fibrosisatrial fibrillationangiotensin IIendoplasmic reticulum stresshydrogen sulfidewarburg effect |
| spellingShingle | Heng-Jing Hu Heng-Jing Hu Xiu-Heng Wang Yao Liu Tian-Qing Zhang Zheng-Rong Chen Chi Zhang Zhi-Han Tang Shun-Lin Qu Hui-Fang Tang Zhi-Sheng Jiang Zhi-Sheng Jiang Zhi-Sheng Jiang Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress Frontiers in Pharmacology atrial fibrosis atrial fibrillation angiotensin II endoplasmic reticulum stress hydrogen sulfide warburg effect |
| title | Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress |
| title_full | Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress |
| title_fullStr | Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress |
| title_full_unstemmed | Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress |
| title_short | Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress |
| title_sort | hydrogen sulfide ameliorates angiotensin ii induced atrial fibrosis progression to atrial fibrillation through inhibition of the warburg effect and endoplasmic reticulum stress |
| topic | atrial fibrosis atrial fibrillation angiotensin II endoplasmic reticulum stress hydrogen sulfide warburg effect |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.690371/full |
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