Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis
Autoimmune myocarditis, which falls within the broad spectrum of myocarditis, is characterized by an excessive inflammatory response in the heart, and can progress into dilated cardiomyopathy and irreversible heart failure in all possibility. However, effective clinical therapeutics are limited due...
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Elsevier
2024-01-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223017614 |
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| author | Chao Lv Chongqing Hu Chuanmeng Zhu Xiaoning Wan Chen Chen Xinyun Ji Yating Qin Li Lu Xiaomei Guo |
| author_facet | Chao Lv Chongqing Hu Chuanmeng Zhu Xiaoning Wan Chen Chen Xinyun Ji Yating Qin Li Lu Xiaomei Guo |
| author_sort | Chao Lv |
| collection | DOAJ |
| description | Autoimmune myocarditis, which falls within the broad spectrum of myocarditis, is characterized by an excessive inflammatory response in the heart, and can progress into dilated cardiomyopathy and irreversible heart failure in all possibility. However, effective clinical therapeutics are limited due to its complex inflammatory reactions. Empagliflozin (EMPA) has been previously demonstrated to possess anti-inflammatory properties. This study aimed to determine the improvement effects of EMPA on cardiac dysfunction under the condition of autoimmune myocarditis, and to further investigate the potential mechanisms. In vivo, all male Balb/c mice were randomly divided into four groups: control, experimental autoimmune myocarditis (EAM), EAM+EMPA and EMPA. In vitro, the effects of EMPA on IL-18-stimulated H9C2 cells were explored and the underlying molecular mechanisms were further determined. EMPA treatment significantly inhibited the development of autoimmune myocarditis, and mice treated with EMPA exhibited improved cardiac function compared with that in the EAM group, potentially through modulating pyroptosis of myocardium. Specifically, the NF-κB pathway was activated in the hearts of the EAM mice, which further activated NLRP3 inflammasome-dependent pyroptosis. EMPA treatment significantly inhibited such activation, thus alleviating inflammatory reactions in the context of EAM. Moreover, in vitro, we also observed that EMPA significantly inhibited pyroptosis of IL-18-stimulated H9C2 cells, and reduced nuclear translocation of NF-κB and degradation of activated IκBα. This work provides the first direct evidence that EMPA can inhibit myocardial inflammation and improve cardiac function in EAM mice, partly attributed to the drug-induced suppression of cardiomyocyte pyroptosis via disrupting the NF-κB pathway. |
| first_indexed | 2024-03-08T16:33:42Z |
| format | Article |
| id | doaj.art-da38fe490b9247e4a21b5f51e9ed4684 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-08T16:33:42Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
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| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-da38fe490b9247e4a21b5f51e9ed46842024-01-06T04:37:45ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-01-01170115963Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosisChao Lv0Chongqing Hu1Chuanmeng Zhu2Xiaoning Wan3Chen Chen4Xinyun Ji5Yating Qin6Li Lu7Xiaomei Guo8Department of Cardiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, ChinaDepartment of Cardiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, ChinaDepartment of Cardiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, ChinaDepartment of Cardiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, ChinaDepartment of Cardiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, ChinaDepartment of Cardiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China; Corresponding authors.Department of Orthopedics, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China; Corresponding authors.Department of Cardiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China; Corresponding authors.Autoimmune myocarditis, which falls within the broad spectrum of myocarditis, is characterized by an excessive inflammatory response in the heart, and can progress into dilated cardiomyopathy and irreversible heart failure in all possibility. However, effective clinical therapeutics are limited due to its complex inflammatory reactions. Empagliflozin (EMPA) has been previously demonstrated to possess anti-inflammatory properties. This study aimed to determine the improvement effects of EMPA on cardiac dysfunction under the condition of autoimmune myocarditis, and to further investigate the potential mechanisms. In vivo, all male Balb/c mice were randomly divided into four groups: control, experimental autoimmune myocarditis (EAM), EAM+EMPA and EMPA. In vitro, the effects of EMPA on IL-18-stimulated H9C2 cells were explored and the underlying molecular mechanisms were further determined. EMPA treatment significantly inhibited the development of autoimmune myocarditis, and mice treated with EMPA exhibited improved cardiac function compared with that in the EAM group, potentially through modulating pyroptosis of myocardium. Specifically, the NF-κB pathway was activated in the hearts of the EAM mice, which further activated NLRP3 inflammasome-dependent pyroptosis. EMPA treatment significantly inhibited such activation, thus alleviating inflammatory reactions in the context of EAM. Moreover, in vitro, we also observed that EMPA significantly inhibited pyroptosis of IL-18-stimulated H9C2 cells, and reduced nuclear translocation of NF-κB and degradation of activated IκBα. This work provides the first direct evidence that EMPA can inhibit myocardial inflammation and improve cardiac function in EAM mice, partly attributed to the drug-induced suppression of cardiomyocyte pyroptosis via disrupting the NF-κB pathway.http://www.sciencedirect.com/science/article/pii/S0753332223017614EmpagliflozinAutoimmune myocarditisPyroptosisIL-18Positive feedback |
| spellingShingle | Chao Lv Chongqing Hu Chuanmeng Zhu Xiaoning Wan Chen Chen Xinyun Ji Yating Qin Li Lu Xiaomei Guo Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis Biomedicine & Pharmacotherapy Empagliflozin Autoimmune myocarditis Pyroptosis IL-18 Positive feedback |
| title | Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis |
| title_full | Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis |
| title_fullStr | Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis |
| title_full_unstemmed | Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis |
| title_short | Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis |
| title_sort | empagliflozin alleviates the development of autoimmune myocarditis via inhibiting nf κb dependent cardiomyocyte pyroptosis |
| topic | Empagliflozin Autoimmune myocarditis Pyroptosis IL-18 Positive feedback |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223017614 |
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