β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β
Shengen Liao,1,* Yuan Tang,1,* Xin Yue,1 Rongrong Gao,1 Wenming Yao,1 Yanli Zhou,1 Haifeng Zhang2,3 1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China; 2Department of Cardiolog...
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2021
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oai:doaj.org-article:e8b967e228a642ebb78fd64f8ed986812021-12-02T17:21:54Zβ-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β1178-7031https://doaj.org/article/e8b967e228a642ebb78fd64f8ed986812021-09-01T00:00:00Zhttps://www.dovepress.com/-hydroxybutyrate-mitigated-heart-failure-with-preserved-ejection-fract-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Shengen Liao,1,* Yuan Tang,1,* Xin Yue,1 Rongrong Gao,1 Wenming Yao,1 Yanli Zhou,1 Haifeng Zhang2,3 1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China; 2Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, People’s Republic of China; 3Department of Cardiology, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haifeng ZhangDepartment of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, People’s Republic of ChinaEmail haifeng_zhang@163.comBackground: This study was designed to investigate the cardioprotective role of β-hydroxybutyrate (BHB) in heart failure with preserved ejection fraction (HFpEF) and the underlying mechanism.Methods: A two-hit model with a high-fat diet (HFD) and Nω-nitrol-arginine methyl ester (L-NAME) was used as an HFpEF model. The treatment group received a weekly intraperitoneal injection of β-hydroxybutyrate (BHB). Cardiac function, inflammation, and fibrosis were evaluated. CD3+CD4+Foxp3+ positive cells within the myocardium were quantified by flow cytometry. The NADPH oxidase 2 (NOX2)/glycogen synthase kinase-3β (GSK3β) pathway was examined by immunoblot analysis.Results: BHB improved diastolic function, fibrosis and cardiac remodeling in HFpEF. Additionally, BHB inhibited cardiac inflammation and increased cardiac Treg cells, which could be due to the downregulation of the NOX2/GSK-3β pathway.Conclusion: BHB protected against the progression of HFpEF by increasing cardiac Treg cells by modulating the NOX2/GSK-3β pathway.Keywords: β-hydroxybutyrate, HFpEF, Treg cells, NOX2, GSK-3βLiao STang YYue XGao RYao WZhou YZhang HDove Medical Pressarticleβ-hydroxybutyratehfpeftreg cellsnox2gsk-3βPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4697-4706 (2021) |
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β-hydroxybutyrate hfpef treg cells nox2 gsk-3β Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
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β-hydroxybutyrate hfpef treg cells nox2 gsk-3β Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Liao S Tang Y Yue X Gao R Yao W Zhou Y Zhang H β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β |
| description |
Shengen Liao,1,* Yuan Tang,1,* Xin Yue,1 Rongrong Gao,1 Wenming Yao,1 Yanli Zhou,1 Haifeng Zhang2,3 1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China; 2Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, People’s Republic of China; 3Department of Cardiology, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haifeng ZhangDepartment of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, People’s Republic of ChinaEmail haifeng_zhang@163.comBackground: This study was designed to investigate the cardioprotective role of β-hydroxybutyrate (BHB) in heart failure with preserved ejection fraction (HFpEF) and the underlying mechanism.Methods: A two-hit model with a high-fat diet (HFD) and Nω-nitrol-arginine methyl ester (L-NAME) was used as an HFpEF model. The treatment group received a weekly intraperitoneal injection of β-hydroxybutyrate (BHB). Cardiac function, inflammation, and fibrosis were evaluated. CD3+CD4+Foxp3+ positive cells within the myocardium were quantified by flow cytometry. The NADPH oxidase 2 (NOX2)/glycogen synthase kinase-3β (GSK3β) pathway was examined by immunoblot analysis.Results: BHB improved diastolic function, fibrosis and cardiac remodeling in HFpEF. Additionally, BHB inhibited cardiac inflammation and increased cardiac Treg cells, which could be due to the downregulation of the NOX2/GSK-3β pathway.Conclusion: BHB protected against the progression of HFpEF by increasing cardiac Treg cells by modulating the NOX2/GSK-3β pathway.Keywords: β-hydroxybutyrate, HFpEF, Treg cells, NOX2, GSK-3β |
| format |
article |
| author |
Liao S Tang Y Yue X Gao R Yao W Zhou Y Zhang H |
| author_facet |
Liao S Tang Y Yue X Gao R Yao W Zhou Y Zhang H |
| author_sort |
Liao S |
| title |
β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β |
| title_short |
β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β |
| title_full |
β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β |
| title_fullStr |
β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β |
| title_full_unstemmed |
β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β |
| title_sort |
β-hydroxybutyrate mitigated heart failure with preserved ejection fraction by increasing treg cells via nox2/gsk-3β |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/e8b967e228a642ebb78fd64f8ed98681 |
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