Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation
Background Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. METHODS AND RESU...
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.029470 |
| _version_ | 1827942944866304000 |
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| author | Zeping Qiu Yingze Fan Zhiyan Wang Fanyi Huang Zhuojin Li Zhihong Sun Sha Hua Wei Jin Yanjia Chen |
| author_facet | Zeping Qiu Yingze Fan Zhiyan Wang Fanyi Huang Zhuojin Li Zhihong Sun Sha Hua Wei Jin Yanjia Chen |
| author_sort | Zeping Qiu |
| collection | DOAJ |
| description | Background Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. METHODS AND RESULTS Administration of recombinant catestatin (1.5 mg/kg/d) improved diastolic dysfunction and left ventricular chamber stiffness in transverse aortic constriction mice with deoxycorticosterone acetate pellet implantation, as reflected by Doppler tissue imaging and pressure‐volume loop catheter. Less cardiac hypertrophy and myocardial fibrosis was observed, and transcriptomic analysis revealed downregulation of mitochondrial electron transport chain components after catestatin treatment. Catestatin reversed mitochondrial structural and respiratory chain component abnormality, decreased mitochondrial proton leak, and reactive oxygen species generation in myocardium. Excessive oxidative stress induced by Ru360 abolished catestatin treatment effects on HFpEF‐like cardiomyocytes in vitro, indicating the beneficial role of catestatin in HFpEF as a mitochondrial ETC modulator. The serum concentration of catestatin was tested among 81 patients with HFpEF and 76 non–heart failure controls. Compared with control subjects, serum catestatin concentration was higher in patients with HFpEF and positively correlated with E velocity to mitral annular e′ velocity ratio, indicating a feedback compensation role of catestatin in HFpEF. Conclusions Catestatin protects against diastolic dysfunction in HFpEF through attenuating mitochondrial electron transport chain–derived reactive oxygen species generation. Serum catestatin concentration is elevated in patients with HFpEF, probably as a relatively insufficient but self‐compensatory mechanism. |
| first_indexed | 2024-03-13T10:07:15Z |
| format | Article |
| id | doaj.art-33037247dea041ba91d38110742ea346 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-13T10:07:15Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-33037247dea041ba91d38110742ea3462023-05-22T11:33:49ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-05-0112910.1161/JAHA.123.029470Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species GenerationZeping Qiu0Yingze Fan1Zhiyan Wang2Fanyi Huang3Zhuojin Li4Zhihong Sun5Sha Hua6Wei Jin7Yanjia Chen8Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaDepartment of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaDepartment of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaDepartment of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaDepartment of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaDepartment of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaInstitute of Cardiovascular Diseases Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaDepartment of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaDepartment of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of ChinaBackground Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. METHODS AND RESULTS Administration of recombinant catestatin (1.5 mg/kg/d) improved diastolic dysfunction and left ventricular chamber stiffness in transverse aortic constriction mice with deoxycorticosterone acetate pellet implantation, as reflected by Doppler tissue imaging and pressure‐volume loop catheter. Less cardiac hypertrophy and myocardial fibrosis was observed, and transcriptomic analysis revealed downregulation of mitochondrial electron transport chain components after catestatin treatment. Catestatin reversed mitochondrial structural and respiratory chain component abnormality, decreased mitochondrial proton leak, and reactive oxygen species generation in myocardium. Excessive oxidative stress induced by Ru360 abolished catestatin treatment effects on HFpEF‐like cardiomyocytes in vitro, indicating the beneficial role of catestatin in HFpEF as a mitochondrial ETC modulator. The serum concentration of catestatin was tested among 81 patients with HFpEF and 76 non–heart failure controls. Compared with control subjects, serum catestatin concentration was higher in patients with HFpEF and positively correlated with E velocity to mitral annular e′ velocity ratio, indicating a feedback compensation role of catestatin in HFpEF. Conclusions Catestatin protects against diastolic dysfunction in HFpEF through attenuating mitochondrial electron transport chain–derived reactive oxygen species generation. Serum catestatin concentration is elevated in patients with HFpEF, probably as a relatively insufficient but self‐compensatory mechanism.https://www.ahajournals.org/doi/10.1161/JAHA.123.029470catestatindiastolic dysfunctionheart failure with preserved ejection fractionmitochondriareactive oxygen species |
| spellingShingle | Zeping Qiu Yingze Fan Zhiyan Wang Fanyi Huang Zhuojin Li Zhihong Sun Sha Hua Wei Jin Yanjia Chen Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease catestatin diastolic dysfunction heart failure with preserved ejection fraction mitochondria reactive oxygen species |
| title | Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation |
| title_full | Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation |
| title_fullStr | Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation |
| title_full_unstemmed | Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation |
| title_short | Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation |
| title_sort | catestatin protects against diastolic dysfunction by attenuating mitochondrial reactive oxygen species generation |
| topic | catestatin diastolic dysfunction heart failure with preserved ejection fraction mitochondria reactive oxygen species |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.029470 |
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