Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury
Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driv...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2024-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0327 |
| _version_ | 1797294881273544704 |
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| author | Yihua Bei Hongyun Wang Yang Liu Zhuhua Su Xinpeng Li Yujiao Zhu Ziyi Zhang Mingming Yin Chen Chen Lin Li Meng Wei Xiangmin Meng Xuchun Liang Zhenzhen Huang Richard Yang Cao Lei Wang Guoping Li Dragos Cretoiu Junjie Xiao |
| author_facet | Yihua Bei Hongyun Wang Yang Liu Zhuhua Su Xinpeng Li Yujiao Zhu Ziyi Zhang Mingming Yin Chen Chen Lin Li Meng Wei Xiangmin Meng Xuchun Liang Zhenzhen Huang Richard Yang Cao Lei Wang Guoping Li Dragos Cretoiu Junjie Xiao |
| author_sort | Yihua Bei |
| collection | DOAJ |
| description | Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear. We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury. Here, we first observed that regular swimming exercise can markedly increase miR-210 levels in the heart and blood samples of rats and mice. Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases. In 8-week swimming model in wild-type (WT) and miR-210 knockout (KO) rats, we demonstrated that miR-210 was not integral for exercise-induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity. In neonatal rat cardiomyocytes, miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size. Additionally, miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and AC16 cell line, indicating its functional roles in human cardiomyocytes. We further identified miR-210 target genes, cyclin-dependent kinase 10 (CDK10) and ephrin-A3 (EFNA3), that regulate cardiomyocyte proliferation and apoptosis. Finally, miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury. We demonstrated that miR-210 crucially contributed to exercise-driven cardioprotection against I/R injury. In summary, this study elucidates the role of miR-210, an exercise-responsive miRNA, in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth. Furthermore, miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury. Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210, which can alleviate I/R injury and promote cardioprotection. |
| first_indexed | 2024-03-07T21:38:31Z |
| format | Article |
| id | doaj.art-6cdf901c23de48168d31eebefc57662b |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-03-07T21:38:31Z |
| publishDate | 2024-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-6cdf901c23de48168d31eebefc57662b2024-02-26T10:25:23ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742024-01-01710.34133/research.0327Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion InjuryYihua Bei0Hongyun Wang1Yang Liu2Zhuhua Su3Xinpeng Li4Yujiao Zhu5Ziyi Zhang6Mingming Yin7Chen Chen8Lin Li9Meng Wei10Xiangmin Meng11Xuchun Liang12Zhenzhen Huang13Richard Yang Cao14Lei Wang15Guoping Li16Dragos Cretoiu17Junjie Xiao18Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Department of Cardiology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), Shanghai University, Shanghai 200444, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Cardiac Rehabilitation Program, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University/Shanghai Clinical Research Center, Shanghai 200031, China.Department of Rehabilitation Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.Department of Medical Genetics, Carol Davila University of Medicine and Pharmacy, Bucharest 020031, Romania.Institute of Geriatrics ( Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science, Shanghai University, Nantong 226011, China.Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear. We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury. Here, we first observed that regular swimming exercise can markedly increase miR-210 levels in the heart and blood samples of rats and mice. Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases. In 8-week swimming model in wild-type (WT) and miR-210 knockout (KO) rats, we demonstrated that miR-210 was not integral for exercise-induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity. In neonatal rat cardiomyocytes, miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size. Additionally, miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and AC16 cell line, indicating its functional roles in human cardiomyocytes. We further identified miR-210 target genes, cyclin-dependent kinase 10 (CDK10) and ephrin-A3 (EFNA3), that regulate cardiomyocyte proliferation and apoptosis. Finally, miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury. We demonstrated that miR-210 crucially contributed to exercise-driven cardioprotection against I/R injury. In summary, this study elucidates the role of miR-210, an exercise-responsive miRNA, in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth. Furthermore, miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury. Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210, which can alleviate I/R injury and promote cardioprotection.https://spj.science.org/doi/10.34133/research.0327 |
| spellingShingle | Yihua Bei Hongyun Wang Yang Liu Zhuhua Su Xinpeng Li Yujiao Zhu Ziyi Zhang Mingming Yin Chen Chen Lin Li Meng Wei Xiangmin Meng Xuchun Liang Zhenzhen Huang Richard Yang Cao Lei Wang Guoping Li Dragos Cretoiu Junjie Xiao Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury Research |
| title | Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury |
| title_full | Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury |
| title_fullStr | Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury |
| title_full_unstemmed | Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury |
| title_short | Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury |
| title_sort | exercise induced mir 210 promotes cardiomyocyte proliferation and survival and mediates exercise induced cardiac protection against ischemia reperfusion injury |
| url | https://spj.science.org/doi/10.34133/research.0327 |
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