Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis
Abstract NOD-like receptor (NLR) family proteins are implicated in various cardiovascular diseases. However, the precise role of NLRC5, the largest member of this family, in myocardial infarction (MI) remains poorly understood. This study reveals that NLRC5 is upregulated in the hearts of both patie...
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07755-z |
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| author | Lingfeng Gu Sibo Wang Liuhua Zhou Wenjing Wang Yulin Bao Ye He Tongtong Yang Jiateng Sun Qiqi Jiang Tiankai Shan Chong Du Zemu Wang Hao Wang Liping Xie Aihua Gu Yang Zhao Yong Ji Qiming Wang Liansheng Wang |
| author_facet | Lingfeng Gu Sibo Wang Liuhua Zhou Wenjing Wang Yulin Bao Ye He Tongtong Yang Jiateng Sun Qiqi Jiang Tiankai Shan Chong Du Zemu Wang Hao Wang Liping Xie Aihua Gu Yang Zhao Yong Ji Qiming Wang Liansheng Wang |
| author_sort | Lingfeng Gu |
| collection | DOAJ |
| description | Abstract NOD-like receptor (NLR) family proteins are implicated in various cardiovascular diseases. However, the precise role of NLRC5, the largest member of this family, in myocardial infarction (MI) remains poorly understood. This study reveals that NLRC5 is upregulated in the hearts of both patients with MI and MI mice. Silencing NLRC5 in cardiomyocytes impairs cardiac repair and functional recovery, while its overexpression enhances these processes. Furthermore, NLRC5 promotes autophagy in cardiomyocytes, and its protective effects are diminished upon autophagy inhibition. Mechanistically, NLRC5 interacts with CAVIN1, facilitating its degradation and subsequent downregulation of CAV1, which in turn increases the expression of the ATG12-ATG5 complex to stimulate autophagy. Conversely, CAV1 overexpression partially suppresses autophagy and attenuates the improvements in cardiac function observed in NLRC5-overexpressing MI hearts. This study highlights the critical regulatory role of NLRC5 in modulating cardiomyocyte autophagy flux, suggesting that NLRC5 activation may represent a promising therapeutic strategy for MI. |
| format | Article |
| id | doaj-art-80f658bc018144d59a9a47c278d2575c |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-80f658bc018144d59a9a47c278d2575c2025-08-20T02:15:06ZengNature PortfolioCommunications Biology2399-36422025-02-018111710.1038/s42003-025-07755-zTargeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axisLingfeng Gu0Sibo Wang1Liuhua Zhou2Wenjing Wang3Yulin Bao4Ye He5Tongtong Yang6Jiateng Sun7Qiqi Jiang8Tiankai Shan9Chong Du10Zemu Wang11Hao Wang12Liping Xie13Aihua Gu14Yang Zhao15Yong Ji16Qiming Wang17Liansheng Wang18Department of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical UniversityDepartment of Biostatistics, School of Public Health, China International Cooperation Center for Environment and Human Health, Nanjing Medical UniversityKey Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract NOD-like receptor (NLR) family proteins are implicated in various cardiovascular diseases. However, the precise role of NLRC5, the largest member of this family, in myocardial infarction (MI) remains poorly understood. This study reveals that NLRC5 is upregulated in the hearts of both patients with MI and MI mice. Silencing NLRC5 in cardiomyocytes impairs cardiac repair and functional recovery, while its overexpression enhances these processes. Furthermore, NLRC5 promotes autophagy in cardiomyocytes, and its protective effects are diminished upon autophagy inhibition. Mechanistically, NLRC5 interacts with CAVIN1, facilitating its degradation and subsequent downregulation of CAV1, which in turn increases the expression of the ATG12-ATG5 complex to stimulate autophagy. Conversely, CAV1 overexpression partially suppresses autophagy and attenuates the improvements in cardiac function observed in NLRC5-overexpressing MI hearts. This study highlights the critical regulatory role of NLRC5 in modulating cardiomyocyte autophagy flux, suggesting that NLRC5 activation may represent a promising therapeutic strategy for MI.https://doi.org/10.1038/s42003-025-07755-z |
| spellingShingle | Lingfeng Gu Sibo Wang Liuhua Zhou Wenjing Wang Yulin Bao Ye He Tongtong Yang Jiateng Sun Qiqi Jiang Tiankai Shan Chong Du Zemu Wang Hao Wang Liping Xie Aihua Gu Yang Zhao Yong Ji Qiming Wang Liansheng Wang Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis Communications Biology |
| title | Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis |
| title_full | Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis |
| title_fullStr | Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis |
| title_full_unstemmed | Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis |
| title_short | Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis |
| title_sort | targeting nlrc5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the cavin1 cav1 axis |
| url | https://doi.org/10.1038/s42003-025-07755-z |
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