MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4
Abstract Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated wi...
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57206-8 |
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| author | Jianbing Zhu Qian Wang Zeqi Zheng Leilei Ma Junjie Guo Hongtao Shi Ru Ying Beilei Gao Shanshan Chen Siyang Yu Bin Yuan Xiaoping Peng Junbo Ge |
| author_facet | Jianbing Zhu Qian Wang Zeqi Zheng Leilei Ma Junjie Guo Hongtao Shi Ru Ying Beilei Gao Shanshan Chen Siyang Yu Bin Yuan Xiaoping Peng Junbo Ge |
| author_sort | Jianbing Zhu |
| collection | DOAJ |
| description | Abstract Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases. |
| first_indexed | 2024-04-24T19:57:24Z |
| format | Article |
| id | doaj.art-b023433ff989494c81560f2729f2298f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:57:24Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b023433ff989494c81560f2729f2298f2024-03-24T12:18:56ZengNature PortfolioScientific Reports2045-23222024-03-0114111410.1038/s41598-024-57206-8MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4Jianbing Zhu0Qian Wang1Zeqi Zheng2Leilei Ma3Junjie Guo4Hongtao Shi5Ru Ying6Beilei Gao7Shanshan Chen8Siyang Yu9Bin Yuan10Xiaoping Peng11Junbo Ge12Department of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Blood Transfusion, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Affiliated Hospital of Qingdao UniversityDepartment of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanchang UniversityDepartment of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan UniversityAbstract Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases.https://doi.org/10.1038/s41598-024-57206-8Myocardial infarction (MI)Mitochondrial fissionmiR-181aProgrammed cell death protein 4 (PDCD4)Bidp53 |
| spellingShingle | Jianbing Zhu Qian Wang Zeqi Zheng Leilei Ma Junjie Guo Hongtao Shi Ru Ying Beilei Gao Shanshan Chen Siyang Yu Bin Yuan Xiaoping Peng Junbo Ge MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4 Scientific Reports Myocardial infarction (MI) Mitochondrial fission miR-181a Programmed cell death protein 4 (PDCD4) Bid p53 |
| title | MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4 |
| title_full | MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4 |
| title_fullStr | MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4 |
| title_full_unstemmed | MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4 |
| title_short | MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4 |
| title_sort | mir 181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4 |
| topic | Myocardial infarction (MI) Mitochondrial fission miR-181a Programmed cell death protein 4 (PDCD4) Bid p53 |
| url | https://doi.org/10.1038/s41598-024-57206-8 |
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