Exercise training attenuates cardiac dysfunction induced by excessive sympathetic activation through an AMPK-KLF4-FMO2 axis.

IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Journal of molecular and cellular cardiology Pub Date : 2024-11-02 DOI:10.1016/j.yjmcc.2024.10.015
Shiyu Fan, Mingming Zhao, Kang Wang, Yawen Deng, Xiaoyue Yu, Ketao Ma, Youyi Zhang, Han Xiao
{"title":"Exercise training attenuates cardiac dysfunction induced by excessive sympathetic activation through an AMPK-KLF4-FMO2 axis.","authors":"Shiyu Fan, Mingming Zhao, Kang Wang, Yawen Deng, Xiaoyue Yu, Ketao Ma, Youyi Zhang, Han Xiao","doi":"10.1016/j.yjmcc.2024.10.015","DOIUrl":null,"url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide and are associated with an overactivated sympathetic system. Although exercise training has shown promise in mitigating sympathetic stress-induced cardiac remodeling, the precise mechanisms remain elusive. Here, we demonstrate that exercise significantly upregulates cardiac flavin-containing monooxygenase 2 (FMO2) expression. Notably, we find that exercise training effectively counteracts sympathetic overactivation-induced cardiac dysfunction and fibrosis by enhancing FMO2 expression via adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Functional investigations employing FMO2 knockdown with adeno-associated virus 9 (AAV9) underscore the necessity for FMO2 expression to protect the heart during exercise in vivo. Furthermore, we identify the krüppel-like factor 4 (KLF4) as a transcriptional mediator of FMO2 that is crucial for the mechanism through which AMPK activation protects against sympathetic overactivation-induced cardiac dysfunction and fibrosis. Taken together, our study reveals a cardioprotective mechanism for exercise training through an AMPK-KLF4-FMO2 signaling pathway that underscores how exercise alleviates cardiac dysfunction induced by excessive sympathetic activation.</p>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of molecular and cellular cardiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.yjmcc.2024.10.015","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0

Abstract

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide and are associated with an overactivated sympathetic system. Although exercise training has shown promise in mitigating sympathetic stress-induced cardiac remodeling, the precise mechanisms remain elusive. Here, we demonstrate that exercise significantly upregulates cardiac flavin-containing monooxygenase 2 (FMO2) expression. Notably, we find that exercise training effectively counteracts sympathetic overactivation-induced cardiac dysfunction and fibrosis by enhancing FMO2 expression via adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Functional investigations employing FMO2 knockdown with adeno-associated virus 9 (AAV9) underscore the necessity for FMO2 expression to protect the heart during exercise in vivo. Furthermore, we identify the krüppel-like factor 4 (KLF4) as a transcriptional mediator of FMO2 that is crucial for the mechanism through which AMPK activation protects against sympathetic overactivation-induced cardiac dysfunction and fibrosis. Taken together, our study reveals a cardioprotective mechanism for exercise training through an AMPK-KLF4-FMO2 signaling pathway that underscores how exercise alleviates cardiac dysfunction induced by excessive sympathetic activation.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
通过AMPK-KLF4-FMO2轴,运动训练可减轻交感神经过度激活引起的心脏功能障碍。
心血管疾病(CVD)是导致全球死亡的主要原因,与交感神经系统过度激活有关。虽然运动训练有望减轻交感神经压力诱导的心脏重塑,但其确切机制仍难以捉摸。在这里,我们证明了运动能显著上调心脏含黄素单加氧酶 2(FMO2)的表达。值得注意的是,我们发现运动训练可通过激活腺苷-5'-单磷酸(AMP)激活蛋白激酶(AMPK)来提高FMO2的表达,从而有效抵消交感神经过度激活诱导的心功能障碍和纤维化。利用腺相关病毒9(AAV9)敲除FMO2的功能研究强调了FMO2的表达对于在体内运动时保护心脏的必要性。此外,我们还发现克鲁佩尔样因子 4(KLF4)是 FMO2 的转录介质,对于 AMPK 激活保护交感神经过度激活诱发的心脏功能障碍和纤维化的机制至关重要。综上所述,我们的研究揭示了运动训练通过 AMPK-KLF4-FMO2 信号通路保护心脏的机制,强调了运动如何缓解交感神经过度激活诱导的心脏功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
10.70
自引率
0.00%
发文量
171
审稿时长
42 days
期刊介绍: The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; bioengineering; computational modeling and systems analysis; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.
期刊最新文献
Exercise training attenuates cardiac dysfunction induced by excessive sympathetic activation through an AMPK-KLF4-FMO2 axis. Different effects of cardiomyocyte contractile activity on transverse and axial tubular system luminal content dynamics. Editorial Board Macrophages in the infarcted heart acquire a fibrogenic phenotype, expressing matricellular proteins, but do not undergo fibroblast conversion Cardiac macrophages and fibroblasts: A synergistic partnership without cellular transition
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1