Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis
Background Pyroptosis is a novel kind of programmed cell death and Caspase-1 plays key roles in driving pyroptosis. The current study aims to elucidate the molecular mechanism affecting cardiomyocyte pyroptosis in myocardial ischemia/reperfusion (I/R) injury, both in vivo and in vitro.Methods A muri...
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Taylor & Francis Group
2025-12-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10641963.2025.2506619 |
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| author | ChenKai Hu FengXia Yuan YingXing Wu Shan Xiao Yuan Xu Xiang Peng Lei He |
| author_facet | ChenKai Hu FengXia Yuan YingXing Wu Shan Xiao Yuan Xu Xiang Peng Lei He |
| author_sort | ChenKai Hu |
| collection | DOAJ |
| description | Background Pyroptosis is a novel kind of programmed cell death and Caspase-1 plays key roles in driving pyroptosis. The current study aims to elucidate the molecular mechanism affecting cardiomyocyte pyroptosis in myocardial ischemia/reperfusion (I/R) injury, both in vivo and in vitro.Methods A murine model of myocardial I/R injury was established and then treated with lentivirus-mediated shRNA targeting Caspase-1 to evaluate the effect of Caspase-1 on myocardial I/R injury. Further, Caspase-1 was silenced in the cardiomyocytes following hypoxia-reoxygenation (H/R) to detect the function of Caspase-1 in mitochondrial homeostasis and cardiomyocyte pyroptosis.Results Knockdown of Caspase-1 inhibited the secretion of interleukin-1 beta (IL-1β), improved cardiac dysfunction and decreased pyroptosis in vivo. The cardio-protective effect was verified in the H/R-induced cardiomyocyte model. Recombinant IL-1β protein reversed the inhibitory effect of Caspase-1 knockdown on pyroptosis.Conclusion Overall, activating the Caspase-1/IL-1β axis by myocardial I/R injury causes mitochondrial homeostasis imbalance, pyroptosis, and the consequent cardiomyocyte injury. |
| format | Article |
| id | doaj-art-29cd2b6573cf41548b49ea93632992ad |
| institution | Kabale University |
| issn | 1064-1963 1525-6006 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Clinical and Experimental Hypertension |
| spelling | doaj-art-29cd2b6573cf41548b49ea93632992ad2025-08-20T03:49:17ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062025-12-0147110.1080/10641963.2025.2506619Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of PyroptosisChenKai Hu0FengXia Yuan1YingXing Wu2Shan Xiao3Yuan Xu4Xiang Peng5Lei He6Department of Cardiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, ChinaDepartment of Pharmacy, the Second Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, ChinaMedical Big Data Research Center, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, ChinaInformation Department, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, ChinaDepartment of Cardiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, ChinaBackground Pyroptosis is a novel kind of programmed cell death and Caspase-1 plays key roles in driving pyroptosis. The current study aims to elucidate the molecular mechanism affecting cardiomyocyte pyroptosis in myocardial ischemia/reperfusion (I/R) injury, both in vivo and in vitro.Methods A murine model of myocardial I/R injury was established and then treated with lentivirus-mediated shRNA targeting Caspase-1 to evaluate the effect of Caspase-1 on myocardial I/R injury. Further, Caspase-1 was silenced in the cardiomyocytes following hypoxia-reoxygenation (H/R) to detect the function of Caspase-1 in mitochondrial homeostasis and cardiomyocyte pyroptosis.Results Knockdown of Caspase-1 inhibited the secretion of interleukin-1 beta (IL-1β), improved cardiac dysfunction and decreased pyroptosis in vivo. The cardio-protective effect was verified in the H/R-induced cardiomyocyte model. Recombinant IL-1β protein reversed the inhibitory effect of Caspase-1 knockdown on pyroptosis.Conclusion Overall, activating the Caspase-1/IL-1β axis by myocardial I/R injury causes mitochondrial homeostasis imbalance, pyroptosis, and the consequent cardiomyocyte injury.https://www.tandfonline.com/doi/10.1080/10641963.2025.2506619Myocardial ischemia/reperfusion injurycaspase-1IL-1βpyroptosismitochondrial homeostasiscardiomyocyte injury |
| spellingShingle | ChenKai Hu FengXia Yuan YingXing Wu Shan Xiao Yuan Xu Xiang Peng Lei He Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis Clinical and Experimental Hypertension Myocardial ischemia/reperfusion injury caspase-1 IL-1β pyroptosis mitochondrial homeostasis cardiomyocyte injury |
| title | Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis |
| title_full | Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis |
| title_fullStr | Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis |
| title_full_unstemmed | Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis |
| title_short | Disruption of the caspase-1/IL-1β axis alleviates myocardial Ischemia/Reperfusion injury via improvement of mitochondrial homeostasis and reduction of Pyroptosis |
| title_sort | disruption of the caspase 1 il 1β axis alleviates myocardial ischemia reperfusion injury via improvement of mitochondrial homeostasis and reduction of pyroptosis |
| topic | Myocardial ischemia/reperfusion injury caspase-1 IL-1β pyroptosis mitochondrial homeostasis cardiomyocyte injury |
| url | https://www.tandfonline.com/doi/10.1080/10641963.2025.2506619 |
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