GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes
Abstract Background Heart failure (HF) seriously threatens human health worldwide. However, the pathological mechanisms underlying HF are still not fully clear. Results In this study, we performed proteomics and transcriptomics analyses on samples from human HF patients and healthy donors to obtain...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-023-01168-3 |
| _version_ | 1797413872240427008 |
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| author | Hongfei Xu Zhen Wang Yalin Wang Shaobo Pan Wenting Zhao Miao Chen Xiaofan Chen Tingting Tao Liang Ma Yiming Ni Weidong Li |
| author_facet | Hongfei Xu Zhen Wang Yalin Wang Shaobo Pan Wenting Zhao Miao Chen Xiaofan Chen Tingting Tao Liang Ma Yiming Ni Weidong Li |
| author_sort | Hongfei Xu |
| collection | DOAJ |
| description | Abstract Background Heart failure (HF) seriously threatens human health worldwide. However, the pathological mechanisms underlying HF are still not fully clear. Results In this study, we performed proteomics and transcriptomics analyses on samples from human HF patients and healthy donors to obtain an overview of the detailed changes in protein and mRNA expression that occur during HF. We found substantial differences in protein expression changes between the atria and ventricles of myocardial tissues from patients with HF. Interestingly, the metabolic state of ventricular tissues was altered in HF samples, and inflammatory pathways were activated in atrial tissues. Through analysis of differentially expressed genes in HF samples, we found that several glutathione S-transferase (GST) family members, especially glutathione S-transferase M2-2 (GSTM2), were decreased in all the ventricular samples. Furthermore, GSTM2 overexpression effectively relieved the progression of cardiac hypertrophy in a transverse aortic constriction (TAC) surgery-induced HF mouse model. Moreover, we found that GSTM2 attenuated DNA damage and extrachromosomal circular DNA (eccDNA) production in cardiomyocytes, thereby ameliorating interferon-I-stimulated macrophage inflammation in heart tissues. Conclusions Our study establishes a proteomic and transcriptomic map of human HF tissues, highlights the functional importance of GSTM2 in HF progression, and provides a novel therapeutic target for HF. |
| first_indexed | 2024-03-09T05:24:17Z |
| format | Article |
| id | doaj.art-645721425efd46d3a712eb8921ffdc69 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-03-09T05:24:17Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-645721425efd46d3a712eb8921ffdc692023-12-03T12:37:44ZengBMCCell & Bioscience2045-37012023-11-0113111610.1186/s13578-023-01168-3GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytesHongfei Xu0Zhen Wang1Yalin Wang2Shaobo Pan3Wenting Zhao4Miao Chen5Xiaofan Chen6Tingting Tao7Liang Ma8Yiming Ni9Weidong Li10Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Operation Room, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Operation Room, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiology, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, School of MedicineAbstract Background Heart failure (HF) seriously threatens human health worldwide. However, the pathological mechanisms underlying HF are still not fully clear. Results In this study, we performed proteomics and transcriptomics analyses on samples from human HF patients and healthy donors to obtain an overview of the detailed changes in protein and mRNA expression that occur during HF. We found substantial differences in protein expression changes between the atria and ventricles of myocardial tissues from patients with HF. Interestingly, the metabolic state of ventricular tissues was altered in HF samples, and inflammatory pathways were activated in atrial tissues. Through analysis of differentially expressed genes in HF samples, we found that several glutathione S-transferase (GST) family members, especially glutathione S-transferase M2-2 (GSTM2), were decreased in all the ventricular samples. Furthermore, GSTM2 overexpression effectively relieved the progression of cardiac hypertrophy in a transverse aortic constriction (TAC) surgery-induced HF mouse model. Moreover, we found that GSTM2 attenuated DNA damage and extrachromosomal circular DNA (eccDNA) production in cardiomyocytes, thereby ameliorating interferon-I-stimulated macrophage inflammation in heart tissues. Conclusions Our study establishes a proteomic and transcriptomic map of human HF tissues, highlights the functional importance of GSTM2 in HF progression, and provides a novel therapeutic target for HF.https://doi.org/10.1186/s13578-023-01168-3Heart failureCardiac hypertrophyProteomicsGlutathione S-transferase M2-2Inflammation |
| spellingShingle | Hongfei Xu Zhen Wang Yalin Wang Shaobo Pan Wenting Zhao Miao Chen Xiaofan Chen Tingting Tao Liang Ma Yiming Ni Weidong Li GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes Cell & Bioscience Heart failure Cardiac hypertrophy Proteomics Glutathione S-transferase M2-2 Inflammation |
| title | GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes |
| title_full | GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes |
| title_fullStr | GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes |
| title_full_unstemmed | GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes |
| title_short | GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes |
| title_sort | gstm2 alleviates heart failure by inhibiting dna damage in cardiomyocytes |
| topic | Heart failure Cardiac hypertrophy Proteomics Glutathione S-transferase M2-2 Inflammation |
| url | https://doi.org/10.1186/s13578-023-01168-3 |
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