Exercise-derived peptide protects against pathological cardiac remodeling

doi:10.1016/j.ebiom.2022.104164

	Exercise-derived peptide protects against pathological cardiac remodeling
	Yin, Anwen 1; Yuan, Ruosen 1; Xiao, Qingqing 1; Zhang, Weifeng 1; Xu, Ke 1; Yang, Xiaoxiao 1; Yang, Wentao 1; Xu, Lei 1; Wang, Xia 1; Zhuang, Fei 1; Li, Yi 1; Cai, Zhaohua 1; Sun, Zhe3 ; Zhou, Bin 2; He, Ben 1; Shen, Linghong 1
	2022-08
发表期刊	EBIOMEDICINE (IF:9.7[JCR-2023],9.2[5-Year])
ISSN	2352-3964
卷号	82
发表状态	已发表
DOI	10.1016/j.ebiom.2022.104164
摘要	["Background Exercise training protects the heart against pathological cardiac remodeling and confers cardioprotection from heart failure. However, the underlying mechanism is still elusive.","Methods An integrative analysis of multi-omics data of the skeletal muscle in response to exercise is performed to search for potential exerkine. Then, CCDC80tide is examined in humans after acute exercise. The role of CCDC80tide is assessed in a mouse model of hypertensive cardiac remodeling and in hypertension-mediated cell injury models. The transcriptomic analysis and immunoprecipitation assay are conducted to explore the mechanism.","Findings The coiled-coil domain-containing protein 80 (CCDC80) is found strongly positively associated with exercise. Interestingly, exercise stimuli induce the secretion of C-terminal CCDC80 (referred as CCDC80tide hereafter) via EVs-encapsulated CCDC80tide into the circulation. Importantly, cardiac-specific expression of CCDC80tide protects against angiotensin II (Ang II)-induced cardiac hypertrophy and fibrosis in mice. In in vitro studies, the expression of CCDC80tide reduces Ang II-induced cardiomyocyte hypertrophy, cardiac microvascular endothelial cell (CMEC) inflammation, and mitigated vascular smooth muscle cell (VSMC) proliferation and collagen formation. To understand the cardioprotective effect of CCDC80tide, a transcriptomic analysis reveals a dramatic inhibition of the STAT3 (Signal transducer and activator of transcription 3) signaling pathway in CCDC80tide overexpressing cells. Mechanistically, CCDC80tide selectively interacts with the kinase-active form of JAK2 (Janus kinase 2) and consequently inhibits its kinase activity to phosphorylate and activate STAT3.","Interpretation The results provide new insights into exercise-afforded cardioprotection in pathological cardiac remodeling and highlight the therapeutic potential of CCDC80tide in heart failure treatment. Copyright (C) 2022 The Author(s). Published by Elsevier B.V."]
关键词	Cardiac remodeling Exercise training Exerkines STAT3 signaling pathway
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China["81770428","81830010","82130012","81900438","82100447"] ; Shanghai Science and Technology Committee["21S11903000","19JC1415702"] ; Emerging and Advanced Technology Programs of Hospital Development Center of Shanghai[SHDC12018129] ; China Postdoctoral Science Foundation[2021M692108] ; China National Postdoctoral Program for Innovative Talents[BX20200211]
WOS研究方向	General & Internal Medicine ; Research & Experimental Medicine
WOS类目	Medicine, General & Internal ; Medicine, Research & Experimental
WOS记录号	WOS:000830983200002
出版者	ELSEVIER
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/214775
专题	生命科学与技术学院_PI研究组_刘冀珑组
通讯作者	He, Ben; Shen, Linghong
作者单位	1.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Cardiol, Sch Med, 241 West Huaihai Rd, Shanghai 200030, Peoples R China 2.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai, Peoples R China 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Yin, Anwen,Yuan, Ruosen,Xiao, Qingqing,et al. Exercise-derived peptide protects against pathological cardiac remodeling[J]. EBIOMEDICINE,2022,82.
APA	Yin, Anwen.,Yuan, Ruosen.,Xiao, Qingqing.,Zhang, Weifeng.,Xu, Ke.,...&Shen, Linghong.(2022).Exercise-derived peptide protects against pathological cardiac remodeling.EBIOMEDICINE,82.
MLA	Yin, Anwen,et al."Exercise-derived peptide protects against pathological cardiac remodeling".EBIOMEDICINE 82(2022).