Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 Axis
Background Therapeutic hypothermia has a beneficial effect on cardiac function after acute myocardial infarction, but the exact mechanism is still unclear. Recent research has suggested that microRNAs participate in acute myocardial infarction to regulate cardiomyocyte survival. This study aimed to...
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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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.122.026160 |
| _version_ | 1827976748551110656 |
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| author | Qiqi Xue Qianru Zhang Zhenzhen Guo Liping Wu Yafen Chen Zhongli Chen Ke Yang Jiumei Cao |
| author_facet | Qiqi Xue Qianru Zhang Zhenzhen Guo Liping Wu Yafen Chen Zhongli Chen Ke Yang Jiumei Cao |
| author_sort | Qiqi Xue |
| collection | DOAJ |
| description | Background Therapeutic hypothermia has a beneficial effect on cardiac function after acute myocardial infarction, but the exact mechanism is still unclear. Recent research has suggested that microRNAs participate in acute myocardial infarction to regulate cardiomyocyte survival. This study aimed to explore the ability of hypothermia‐regulated microRNA‐483‐3p (miR‐483‐3p) to inhibit hypoxia‐induced myocardial infarction. Methods and Results Primary cardiomyocytes were cultured under hypoxia at 32 °C to mimic therapeutic hypothermia, and the differentially expressed microRNAs were determined by RNA sequencing. Therapeutic hypothermia recovered hypoxia‐induced increases in apoptosis, decreases in ATP levels, and decreases in miR‐483‐3p expression. Overexpression of miR‐483‐3p exhibited effects similar to those of therapeutic hypothermia on hypoxia in the treatment of cardiomyocytes to associate with maintaining the mitochondrial membrane potential, and cyclin‐dependent kinase 9 (Cdk9) was identified as a target gene with downregulated expression by miR‐483‐3p. Knockdown of Cdk9 also promoted cardiac survival, ATP production, and mitochondrial membrane potential stability under hypoxia. In vivo, the expression of miR‐483‐3p and Cdk9 was tested in the cardiac tissue of the mice with acute myocardial infarction, and the expression of miR‐483‐3p decreased and Cdk9 increased in the region of myocardial infarction. However, miR‐483‐3p was overexpressed with lentivirus, which suppressed apoptosis, infarct size (miR‐483‐3p, 22.00±4.04% versus negative control, 28.57±5.44%, P<0.05), and Cdk9 expression to improve cardiac contractility. Conclusions MiR‐483‐3p antagonizes hypoxia, leading to cardiomyocyte injury by targeting Cdk9, which is a new mechanism of therapeutic hypothermia. |
| first_indexed | 2024-04-09T20:41:30Z |
| format | Article |
| id | doaj.art-be7c9b26e6e64df6a95b19625ad86af2 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-09T20:41:30Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-be7c9b26e6e64df6a95b19625ad86af22023-03-30T03:59:11ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-02-0112410.1161/JAHA.122.026160Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 AxisQiqi Xue0Qianru Zhang1Zhenzhen Guo2Liping Wu3Yafen Chen4Zhongli Chen5Ke Yang6Jiumei Cao7Department of Geriatrics Ruijin Hospital, Shanghai Jiaotong University School of Medicine Shanghai ChinaDepartment of Cardiology Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine Shanghai ChinaDepartment of Cardiovascular Medicine Ruijin Hospital, Shanghai Jiaotong University School of Medicine Shanghai ChinaDepartment of Cardiac Imaging Center The First Affiliated Hospital, Auhui Medical University Hefei ChinaShanghai Institute of Cardiovascular Diseases Zhongshan Hospital, Fudan University Shanghai ChinaState Key Laboratory of Cardiovascular Disease Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Cardiovascular Medicine Ruijin Hospital, Shanghai Jiaotong University School of Medicine Shanghai ChinaDepartment of Geriatrics Ruijin Hospital, Shanghai Jiaotong University School of Medicine Shanghai ChinaBackground Therapeutic hypothermia has a beneficial effect on cardiac function after acute myocardial infarction, but the exact mechanism is still unclear. Recent research has suggested that microRNAs participate in acute myocardial infarction to regulate cardiomyocyte survival. This study aimed to explore the ability of hypothermia‐regulated microRNA‐483‐3p (miR‐483‐3p) to inhibit hypoxia‐induced myocardial infarction. Methods and Results Primary cardiomyocytes were cultured under hypoxia at 32 °C to mimic therapeutic hypothermia, and the differentially expressed microRNAs were determined by RNA sequencing. Therapeutic hypothermia recovered hypoxia‐induced increases in apoptosis, decreases in ATP levels, and decreases in miR‐483‐3p expression. Overexpression of miR‐483‐3p exhibited effects similar to those of therapeutic hypothermia on hypoxia in the treatment of cardiomyocytes to associate with maintaining the mitochondrial membrane potential, and cyclin‐dependent kinase 9 (Cdk9) was identified as a target gene with downregulated expression by miR‐483‐3p. Knockdown of Cdk9 also promoted cardiac survival, ATP production, and mitochondrial membrane potential stability under hypoxia. In vivo, the expression of miR‐483‐3p and Cdk9 was tested in the cardiac tissue of the mice with acute myocardial infarction, and the expression of miR‐483‐3p decreased and Cdk9 increased in the region of myocardial infarction. However, miR‐483‐3p was overexpressed with lentivirus, which suppressed apoptosis, infarct size (miR‐483‐3p, 22.00±4.04% versus negative control, 28.57±5.44%, P<0.05), and Cdk9 expression to improve cardiac contractility. Conclusions MiR‐483‐3p antagonizes hypoxia, leading to cardiomyocyte injury by targeting Cdk9, which is a new mechanism of therapeutic hypothermia.https://www.ahajournals.org/doi/10.1161/JAHA.122.026160cardiomyocytesCdk9hypoxiamicroRNA‐483‐3ptherapeutic hypothermia |
| spellingShingle | Qiqi Xue Qianru Zhang Zhenzhen Guo Liping Wu Yafen Chen Zhongli Chen Ke Yang Jiumei Cao Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 Axis Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiomyocytes Cdk9 hypoxia microRNA‐483‐3p therapeutic hypothermia |
| title | Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 Axis |
| title_full | Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 Axis |
| title_fullStr | Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 Axis |
| title_full_unstemmed | Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 Axis |
| title_short | Therapeutic Hypothermia Inhibits Hypoxia‐Induced Cardiomyocyte Apoptosis Via the MiR‐483‐3p/Cdk9 Axis |
| title_sort | therapeutic hypothermia inhibits hypoxia induced cardiomyocyte apoptosis via the mir 483 3p cdk9 axis |
| topic | cardiomyocytes Cdk9 hypoxia microRNA‐483‐3p therapeutic hypothermia |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.026160 |
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