The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes

doi:10.1016/j.freeradbiomed.2024.09.003

科研成果详情

题名	The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes
作者	Liu, Shuai 1,2,3; Liu, Fu-Zhong 1; Yan, Jue-Yue 4; Fang, Xing 4; Xu, Zhi-Peng 4; Cai, Hong-Liu 4; Yang, Ying-Jun 1; Yu, Yong-Wei 4
发表日期	2024-11-01
发表期刊	Free Radical Biology and Medicine 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Sepsis Elabela Autophagy TFEB Pyroptosis
摘要	Background: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. Materials and methods: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 mu M Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. Results: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. Conclusion: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.
资助项目	First People's Hospital oF Jiashan - Zhejiang Provincial Natural Science Foundation of China [LQ23H020004]; Medical and Health Research Project of Zhejiang Province [2024KY983]
出版者	ELSEVIER SCIENCE INC
ISSN	0891-5849
EISSN	1873-4596
卷号	224 页码:405-417
DOI	10.1016/j.freeradbiomed.2024.09.003
页数	13
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS记录号	WOS:001312172900001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39241986
SCOPUSEID	2-s2.0-85203292468
通讯作者地址	[Yang, Ying-Jun]First Peoples Hosp Jiashan, Dept Cardiol, Tiyu South Rd 1218, Jiaxing 314100, Zhejiang, Peoples R China. ; [Yu, Yong-Wei]Zhejiang Univ, Sch Med, Affiliated Hosp 1, Intens Care Unit, Hangzhou 310003, Peoples R China.
Scopus学科分类	Biochemistry;Physiology (medical)
SCOPUS_ID	SCOPUS_ID:85203292468
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/218653
专题	附属第二医院附属第二医院_耳鼻咽喉科第二临床医学院、附属第二医院、育英儿童医院
通讯作者	Yang, Ying-Jun; Yu, Yong-Wei
作者单位	1.First Peoples Hosp Jiashan, Dept Cardiol, Tiyu South Rd 1218, Jiaxing 314100, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 2, Dept Cardiol, Wenzhou 325000, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325000, Zhejiang, Peoples R China; 4.Zhejiang Univ, Sch Med, Affiliated Hosp 1, Intens Care Unit, Hangzhou 310003, Peoples R China
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 耳鼻咽喉科
推荐引用方式 GB/T 7714	Liu, Shuai,Liu, Fu-Zhong,Yan, Jue-Yue,et al. The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes[J]. Free Radical Biology and Medicine,2024,224:405-417.
APA	Liu, Shuai., Liu, Fu-Zhong., Yan, Jue-Yue., Fang, Xing., Xu, Zhi-Peng., ... & Yu, Yong-Wei. (2024). The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes. Free Radical Biology and Medicine, 224, 405-417.
MLA	Liu, Shuai,et al."The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes".Free Radical Biology and Medicine 224(2024):405-417.