Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity
Abstract It has been reported that growth differentiation factor 11 (GDF11) protects against myocardial ischemia/reperfusion (IR) injury, but the underlying mechanisms have not been fully clarified. Considering that GDF11 plays a role in the aging/rejuvenation process and that aging is associated wi...
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Format: | Article |
Language: | English |
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Nature Publishing Group
2021-07-01
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Series: | Cell Death and Disease |
Online Access: | https://doi.org/10.1038/s41419-021-03954-8 |
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Article |
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DOAJ |
language |
English |
format |
Article |
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DOAJ |
author |
Lin Chen Guangjin Luo Yameng Liu Hairuo Lin Cankun Zheng Dongxiao Xie Yingqi Zhu Lu Chen Xiaoxia Huang Donghong Hu Jiahe Xie Zhenhuan Chen Wangjun Liao Jianping Bin Qiancheng Wang Yulin Liao |
spellingShingle |
Lin Chen Guangjin Luo Yameng Liu Hairuo Lin Cankun Zheng Dongxiao Xie Yingqi Zhu Lu Chen Xiaoxia Huang Donghong Hu Jiahe Xie Zhenhuan Chen Wangjun Liao Jianping Bin Qiancheng Wang Yulin Liao Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity Cell Death and Disease |
author_facet |
Lin Chen Guangjin Luo Yameng Liu Hairuo Lin Cankun Zheng Dongxiao Xie Yingqi Zhu Lu Chen Xiaoxia Huang Donghong Hu Jiahe Xie Zhenhuan Chen Wangjun Liao Jianping Bin Qiancheng Wang Yulin Liao |
author_sort |
Lin Chen |
title |
Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity |
title_short |
Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity |
title_full |
Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity |
title_fullStr |
Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity |
title_full_unstemmed |
Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity |
title_sort |
growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity |
publisher |
Nature Publishing Group |
series |
Cell Death and Disease |
issn |
2041-4889 |
publishDate |
2021-07-01 |
description |
Abstract It has been reported that growth differentiation factor 11 (GDF11) protects against myocardial ischemia/reperfusion (IR) injury, but the underlying mechanisms have not been fully clarified. Considering that GDF11 plays a role in the aging/rejuvenation process and that aging is associated with telomere shortening and cardiac dysfunction, we hypothesized that GDF11 might protect against IR injury by activating telomerase. Human plasma GDF11 levels were significantly lower in acute coronary syndrome patients than in chronic coronary syndrome patients. IR mice with myocardial overexpression GDF11 (oe-GDF11) exhibited a significantly smaller myocardial infarct size, less cardiac remodeling and dysfunction, fewer apoptotic cardiomyocytes, higher telomerase activity, longer telomeres, and higher ATP generation than IR mice treated with an adenovirus carrying a negative control plasmid. Furthermore, mitochondrial biogenesis-related proteins and some antiapoptotic proteins were significantly upregulated by oe-GDF11. These cardioprotective effects of oe-GDF11 were significantly antagonized by BIBR1532, a specific telomerase inhibitor. Similar effects of oe-GDF11 on apoptosis and mitochondrial energy biogenesis were observed in cultured neonatal rat cardiomyocytes, whereas GDF11 silencing elicited the opposite effects to oe-GDF11 in mice. We concluded that telomerase activation by GDF11 contributes to the alleviation of myocardial IR injury through enhancing mitochondrial biogenesis and suppressing cardiomyocyte apoptosis. |
url |
https://doi.org/10.1038/s41419-021-03954-8 |
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doaj-240e0857e62340f087b7f770f36d60652021-07-04T11:05:06ZengNature Publishing GroupCell Death and Disease2041-48892021-07-0112711410.1038/s41419-021-03954-8Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activityLin Chen0Guangjin Luo1Yameng Liu2Hairuo Lin3Cankun Zheng4Dongxiao Xie5Yingqi Zhu6Lu Chen7Xiaoxia Huang8Donghong Hu9Jiahe Xie10Zhenhuan Chen11Wangjun Liao12Jianping Bin13Qiancheng Wang14Yulin Liao15Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Oncology, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Nanfang Hospital, Southern Medical UniversityAbstract It has been reported that growth differentiation factor 11 (GDF11) protects against myocardial ischemia/reperfusion (IR) injury, but the underlying mechanisms have not been fully clarified. Considering that GDF11 plays a role in the aging/rejuvenation process and that aging is associated with telomere shortening and cardiac dysfunction, we hypothesized that GDF11 might protect against IR injury by activating telomerase. Human plasma GDF11 levels were significantly lower in acute coronary syndrome patients than in chronic coronary syndrome patients. IR mice with myocardial overexpression GDF11 (oe-GDF11) exhibited a significantly smaller myocardial infarct size, less cardiac remodeling and dysfunction, fewer apoptotic cardiomyocytes, higher telomerase activity, longer telomeres, and higher ATP generation than IR mice treated with an adenovirus carrying a negative control plasmid. Furthermore, mitochondrial biogenesis-related proteins and some antiapoptotic proteins were significantly upregulated by oe-GDF11. These cardioprotective effects of oe-GDF11 were significantly antagonized by BIBR1532, a specific telomerase inhibitor. Similar effects of oe-GDF11 on apoptosis and mitochondrial energy biogenesis were observed in cultured neonatal rat cardiomyocytes, whereas GDF11 silencing elicited the opposite effects to oe-GDF11 in mice. We concluded that telomerase activation by GDF11 contributes to the alleviation of myocardial IR injury through enhancing mitochondrial biogenesis and suppressing cardiomyocyte apoptosis.https://doi.org/10.1038/s41419-021-03954-8 |