Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients
Background: The prominent mitochondrial metabolic changes of the atrium reportedly have significant impact on electrical signals and structural remodeling which play important roles in the occurrence and development of atrial fibrillation (AF). However, the mechanism is not completely known.Objectiv...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1123391/full |
| _version_ | 1797852951003267072 |
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| author | Weizhuo Liu Bo Hu Yuliang Wang Xiaobin Zhang Miao Zhu Yu Shi Changfa Guo Yangyang Zhang |
| author_facet | Weizhuo Liu Bo Hu Yuliang Wang Xiaobin Zhang Miao Zhu Yu Shi Changfa Guo Yangyang Zhang |
| author_sort | Weizhuo Liu |
| collection | DOAJ |
| description | Background: The prominent mitochondrial metabolic changes of the atrium reportedly have significant impact on electrical signals and structural remodeling which play important roles in the occurrence and development of atrial fibrillation (AF). However, the mechanism is not completely known.Objective: This study was aimed to explore the mitochondrial metabolism reprogrammed in AF patients by integrating metabolomics as well as proteomics of human atrium tissues.Methods and Results: Left atrial tissue samples were harvested from 10 non-valvular AF patients and 10 matched samples from healthy donors for transplantation. In metabolomics analysis, 113 metabolites were upregulated and 10 metabolites were downregulated in AF, where multiple pathways related to mitochondrial energy metabolism were enriched. Correlation analysis between the differentially expressed proteins and metabolites identified several hub proteins related to mitochondrial function including Glycerol-3-phosphate dehydrogenase 2 (GPD2), Synemin (SYNM), Plectin (PLEC), with MCC score of 27, 17, 16, respectively, which have the most interactions with the dysregulated metabolites and ranked at the top in network string interactions scored by MCC method. All 330 differentially expressed proteins including 225 upregulated and 105 downregulated molecules were revealed and analyzed, which identified the downregulation of GPD2 (p = 0.02 and FC = 0.77), PLEC (p < 0.001 and FC = 0.71) and SYNM (p = 0.04 and FC = 0.76) in AF patients. Gene Set Variation Analysis (GSEA) showed mitochondrial metabolism-associated pathways including oxidative phosphorylation (NES: −1.73) and ATP biosynthetic process (NES: −2.29), were dramatically diversified in human AF. In GSVA, the expression levels of GPD2, PLEC, and SYNM were demonstrated to be associated with multiple metabolic pathways related to mitochondrial function (e.g., lipid metabolism and AMP activated protein kinase signaling) and cardiac structural and electrical remodeling (e.g., contractile fiber, ion homeostasis), which were proven vital in the development and maintenance of AF.Conclusion: In all, this study provides new insights into understanding the mechanisms of AF progression, especially the reprogramming mitochondrial metabolism, and identifies several genes related to mitochondrial function as novel targets for AF, which may be involved in the occurrence and development of AF. |
| first_indexed | 2024-04-09T19:42:39Z |
| format | Article |
| id | doaj.art-ed00831ff4e6414e9907ab2e42aa806c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-09T19:42:39Z |
| publishDate | 2023-04-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-ed00831ff4e6414e9907ab2e42aa806c2023-04-04T05:23:12ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-04-011410.3389/fphys.2023.11233911123391Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patientsWeizhuo Liu0Bo Hu1Yuliang Wang2Xiaobin Zhang3Miao Zhu4Yu Shi5Changfa Guo6Yangyang Zhang7Department of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Immunology, Nanjing Medical University, Nanjing, ChinaDepartment of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackground: The prominent mitochondrial metabolic changes of the atrium reportedly have significant impact on electrical signals and structural remodeling which play important roles in the occurrence and development of atrial fibrillation (AF). However, the mechanism is not completely known.Objective: This study was aimed to explore the mitochondrial metabolism reprogrammed in AF patients by integrating metabolomics as well as proteomics of human atrium tissues.Methods and Results: Left atrial tissue samples were harvested from 10 non-valvular AF patients and 10 matched samples from healthy donors for transplantation. In metabolomics analysis, 113 metabolites were upregulated and 10 metabolites were downregulated in AF, where multiple pathways related to mitochondrial energy metabolism were enriched. Correlation analysis between the differentially expressed proteins and metabolites identified several hub proteins related to mitochondrial function including Glycerol-3-phosphate dehydrogenase 2 (GPD2), Synemin (SYNM), Plectin (PLEC), with MCC score of 27, 17, 16, respectively, which have the most interactions with the dysregulated metabolites and ranked at the top in network string interactions scored by MCC method. All 330 differentially expressed proteins including 225 upregulated and 105 downregulated molecules were revealed and analyzed, which identified the downregulation of GPD2 (p = 0.02 and FC = 0.77), PLEC (p < 0.001 and FC = 0.71) and SYNM (p = 0.04 and FC = 0.76) in AF patients. Gene Set Variation Analysis (GSEA) showed mitochondrial metabolism-associated pathways including oxidative phosphorylation (NES: −1.73) and ATP biosynthetic process (NES: −2.29), were dramatically diversified in human AF. In GSVA, the expression levels of GPD2, PLEC, and SYNM were demonstrated to be associated with multiple metabolic pathways related to mitochondrial function (e.g., lipid metabolism and AMP activated protein kinase signaling) and cardiac structural and electrical remodeling (e.g., contractile fiber, ion homeostasis), which were proven vital in the development and maintenance of AF.Conclusion: In all, this study provides new insights into understanding the mechanisms of AF progression, especially the reprogramming mitochondrial metabolism, and identifies several genes related to mitochondrial function as novel targets for AF, which may be involved in the occurrence and development of AF.https://www.frontiersin.org/articles/10.3389/fphys.2023.1123391/fullatrial fibrillationproteomicsmetabolomicsmitochondrial functionmultiple targets |
| spellingShingle | Weizhuo Liu Bo Hu Yuliang Wang Xiaobin Zhang Miao Zhu Yu Shi Changfa Guo Yangyang Zhang Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients Frontiers in Physiology atrial fibrillation proteomics metabolomics mitochondrial function multiple targets |
| title | Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients |
| title_full | Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients |
| title_fullStr | Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients |
| title_full_unstemmed | Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients |
| title_short | Multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients |
| title_sort | multiple targets related to mitochondrial function unveiled by metabolomics and proteomics profiles of hearts from atrial fibrillation patients |
| topic | atrial fibrillation proteomics metabolomics mitochondrial function multiple targets |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1123391/full |
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