机械通气 ICU 患者膈肌萎缩的原因是肌核凋亡。

Wout J. Claassen, Marloes van den Berg, Rianne J Baelde, Sylvia J.P. Bogaards, Luuk Bonis, Heleen C. Hakkeling, Gerben Schaaf, Albertus Beishuizen, Chris Dickhoff, Reinier A. Boon, Leo Heunks, Tyler J. Kirby, Coen A.C. Ottenheijm
{"title":"机械通气 ICU 患者膈肌萎缩的原因是肌核凋亡。","authors":"Wout J. Claassen, Marloes van den Berg, Rianne J Baelde, Sylvia J.P. Bogaards, Luuk Bonis, Heleen C. Hakkeling, Gerben Schaaf, Albertus Beishuizen, Chris Dickhoff, Reinier A. Boon, Leo Heunks, Tyler J. Kirby, Coen A.C. Ottenheijm","doi":"10.1101/2024.07.23.24310792","DOIUrl":null,"url":null,"abstract":"Abstract (236 words)\nRationale. Intensive care unit (ICU) acquired diaphragm weakness is a common consequence of mechanical ventilation (MV). It contributes to difficult weaning, which is associated with increased morbidity and mortality. Diaphragm weakness is caused by a combination of atrophy and dysfunction of myofibers, large syncytial cells that are maintained by a population of myonuclei. Each myonucleus provides gene transcripts to a finite fiber volume, termed the myonuclear domain. Myonuclear loss in myofibers undergoing atrophy is subject to debate. Myonuclear number is a determinant of transcriptional capacity, and therefore critical for muscle regeneration after atrophy. Objectives. Our objective was to investigate if and how myonuclear number is altered in the diaphragm of mechanically ventilated ICU patients. Methods. We used a combination of confocal microscopy, transcriptomics, and immunohistochemistry techniques to study myonuclear alterations in diaphragm and quadriceps biopsies from MV ICU patients. Measurements and Main Results. Patients with established diaphragm atrophy had a reduced myonuclear number and myonuclear domain. Intrinsic apoptotic pathway activation was identified as a potential mechanism underlying myonuclear removal in the diaphragm of mechanically ventilated ICU patients. Total transcription of myofibers decreased with myonuclear loss. Furthermore, muscle stem cell number was reduced in the patients with diaphragm atrophy.\nConclusion. We identified myonuclear loss due to intrinsic apoptotic pathway activation as a mechanism underlying diaphragm atrophy in mechanically ventilated patients. The loss of myonuclei may contribute to difficult weaning due to impaired regrowth of myofibers after atrophy.","PeriodicalId":501249,"journal":{"name":"medRxiv - Intensive Care and Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Myonuclear apoptosis underlies diaphragm atrophy in mechanically ventilated ICU patients.\",\"authors\":\"Wout J. Claassen, Marloes van den Berg, Rianne J Baelde, Sylvia J.P. Bogaards, Luuk Bonis, Heleen C. Hakkeling, Gerben Schaaf, Albertus Beishuizen, Chris Dickhoff, Reinier A. Boon, Leo Heunks, Tyler J. Kirby, Coen A.C. Ottenheijm\",\"doi\":\"10.1101/2024.07.23.24310792\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract (236 words)\\nRationale. Intensive care unit (ICU) acquired diaphragm weakness is a common consequence of mechanical ventilation (MV). It contributes to difficult weaning, which is associated with increased morbidity and mortality. Diaphragm weakness is caused by a combination of atrophy and dysfunction of myofibers, large syncytial cells that are maintained by a population of myonuclei. Each myonucleus provides gene transcripts to a finite fiber volume, termed the myonuclear domain. Myonuclear loss in myofibers undergoing atrophy is subject to debate. Myonuclear number is a determinant of transcriptional capacity, and therefore critical for muscle regeneration after atrophy. Objectives. Our objective was to investigate if and how myonuclear number is altered in the diaphragm of mechanically ventilated ICU patients. Methods. We used a combination of confocal microscopy, transcriptomics, and immunohistochemistry techniques to study myonuclear alterations in diaphragm and quadriceps biopsies from MV ICU patients. Measurements and Main Results. Patients with established diaphragm atrophy had a reduced myonuclear number and myonuclear domain. Intrinsic apoptotic pathway activation was identified as a potential mechanism underlying myonuclear removal in the diaphragm of mechanically ventilated ICU patients. Total transcription of myofibers decreased with myonuclear loss. Furthermore, muscle stem cell number was reduced in the patients with diaphragm atrophy.\\nConclusion. We identified myonuclear loss due to intrinsic apoptotic pathway activation as a mechanism underlying diaphragm atrophy in mechanically ventilated patients. The loss of myonuclei may contribute to difficult weaning due to impaired regrowth of myofibers after atrophy.\",\"PeriodicalId\":501249,\"journal\":{\"name\":\"medRxiv - Intensive Care and Critical Care Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"medRxiv - Intensive Care and Critical Care Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.07.23.24310792\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Intensive Care and Critical Care Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.07.23.24310792","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

摘要(236 个字)理由。重症监护室(ICU)获得性膈肌无力是机械通气(MV)的常见后果。它导致断奶困难,与发病率和死亡率的增加有关。膈肌无力是由肌纤维萎缩和功能障碍共同造成的,肌纤维是由肌核群维持的大型合胞体细胞。每个肌核为有限的纤维体积(称为肌核域)提供基因转录本。肌纤维在萎缩过程中会出现肌核丢失,这一点尚存在争议。肌核数量是转录能力的决定因素,因此对萎缩后的肌肉再生至关重要。研究目的我们的目的是研究机械通气 ICU 患者膈肌的肌核数量是否以及如何发生变化。方法。我们结合使用了共聚焦显微镜、转录组学和免疫组化技术,研究机械通气 ICU 患者膈肌和股四头肌活检组织中肌核的变化。测量和主要结果。膈肌萎缩患者的肌核数量和肌核域减少。内在凋亡途径的激活被认为是导致机械通气 ICU 患者膈肌肌核消失的潜在机制。肌纤维的总转录量随着肌核的丢失而减少。此外,膈肌萎缩患者的肌肉干细胞数量减少。我们发现肌核缺失是机械通气患者膈肌萎缩的内在机制之一。肌核的丢失可能会导致断奶困难,因为萎缩后肌纤维的再生能力受损。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Myonuclear apoptosis underlies diaphragm atrophy in mechanically ventilated ICU patients.
Abstract (236 words) Rationale. Intensive care unit (ICU) acquired diaphragm weakness is a common consequence of mechanical ventilation (MV). It contributes to difficult weaning, which is associated with increased morbidity and mortality. Diaphragm weakness is caused by a combination of atrophy and dysfunction of myofibers, large syncytial cells that are maintained by a population of myonuclei. Each myonucleus provides gene transcripts to a finite fiber volume, termed the myonuclear domain. Myonuclear loss in myofibers undergoing atrophy is subject to debate. Myonuclear number is a determinant of transcriptional capacity, and therefore critical for muscle regeneration after atrophy. Objectives. Our objective was to investigate if and how myonuclear number is altered in the diaphragm of mechanically ventilated ICU patients. Methods. We used a combination of confocal microscopy, transcriptomics, and immunohistochemistry techniques to study myonuclear alterations in diaphragm and quadriceps biopsies from MV ICU patients. Measurements and Main Results. Patients with established diaphragm atrophy had a reduced myonuclear number and myonuclear domain. Intrinsic apoptotic pathway activation was identified as a potential mechanism underlying myonuclear removal in the diaphragm of mechanically ventilated ICU patients. Total transcription of myofibers decreased with myonuclear loss. Furthermore, muscle stem cell number was reduced in the patients with diaphragm atrophy. Conclusion. We identified myonuclear loss due to intrinsic apoptotic pathway activation as a mechanism underlying diaphragm atrophy in mechanically ventilated patients. The loss of myonuclei may contribute to difficult weaning due to impaired regrowth of myofibers after atrophy.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信