Altered muscle transcriptome as molecular basis of long-term muscle weakness in survivors from critical illness.

IF 27.1 1区医学 Q1 CRITICAL CARE MEDICINE

Intensive Care Medicine Pub Date : 2025-06-10 DOI:10.1007/s00134-025-07949-3

Ceren Uzun Ayar, Fabian Güiza, Inge Derese, Lies Pauwels, Sarah Vander Perre, Isabel Pintelon, Michaël Casaer, Nathalie Van Aerde, Greet Hermans, Sarah Derde, Lucas Kreiss, Greet Van den Berghe, Ilse Vanhorebeek

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引用次数: 0

Abstract

Purpose: Critically ill patients requiring intensive care unit (ICU) admission suffer from muscle weakness that persists for years, compromising quality-of-life. The pathophysiology of this long-term weakness remains unclear. We hypothesized that former ICU-patients show a long-term abnormal RNA-expression profile, which may contribute to lower long-term strength and for which modifiable risk factors can be identified.

Methods: This pre-planned secondary analysis of the EPaNIC-trial compared muscle transcriptomes of 115 former ICU-patients 5 years after critical illness and 30 matched controls with RNA-sequencing, followed by pathway over-representation and differential co-expression analyses of the differentially expressed RNAs. We used multivariable linear regression analyses to identify which of the abnormal RNA-expressions associated with the long-term muscle strength of the patients and to identify potential risk factors for the abnormal RNA-expressions.

Results: In former patients, 234 down-regulated and 116 up-regulated RNAs were identified after adjustment for age, sex, and BMI. Pathway over-representation and further molecular and histological analyses indicated impaired mitochondrial energy metabolism, disturbed lipid metabolism, and increased collagen formation/fibrosis in former patients. Abnormal muscle RNA-expression in former patients correlated with lower long-term muscle strength. Several treatments given in-ICU and at 5-year follow-up associated with abnormal RNA-expression, most notably in-ICU early parenteral nutrition (early PN) and glucocorticoid use.

Conclusion: Abnormal RNA-expression profiles 5 years after critical illness suggest disrupted mitochondrial function, disturbed lipid metabolism, and fibrosis, associated with lower long-term muscle strength and partly attributable to possibly avoidable risk factors. These findings open perspectives for prevention and possibly treatment of long-term muscle weakness after critical illness.

Trial registration number and date: ClinicalTrials.gov-NCT00512122, July 31, 2007.

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肌肉转录组改变是危重疾病幸存者长期肌肉无力的分子基础。

目的：需要重症监护病房（ICU）入院的危重患者遭受持续多年的肌肉无力，影响生活质量。这种长期虚弱的病理生理机制尚不清楚。我们假设前icu患者表现出长期异常的rna表达谱，这可能导致长期强度降低，并且可以确定可改变的危险因素。方法：这项预先计划的epanic试验的二次分析比较了115名危重疾病后5年的前icu患者和30名匹配对照者的肌肉转录组，并进行了rna测序，随后对差异表达的rna进行了通路过度表达和差异共表达分析。我们使用多变量线性回归分析来确定哪些异常rna表达与患者的长期肌肉力量相关，并确定异常rna表达的潜在危险因素。结果：在前患者中，在调整年龄、性别和BMI后，鉴定出234个下调rna和116个上调rna。通路过度代表和进一步的分子和组织学分析表明，前患者线粒体能量代谢受损，脂质代谢紊乱，胶原形成/纤维化增加。既往患者肌肉rna表达异常与长期肌力降低相关。在icu和5年随访中接受的几种治疗与异常rna表达相关，最明显的是在icu早期肠外营养（早期PN）和糖皮质激素的使用。结论：危重疾病后5年的异常rna表达谱表明线粒体功能紊乱、脂质代谢紊乱和纤维化与长期肌力降低有关，部分归因于可能可避免的危险因素。这些发现为预防和治疗危重疾病后的长期肌肉无力提供了新的视角。试验注册号和日期：ClinicalTrials.gov-NCT00512122, 2007年7月31日。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Intensive Care Medicine 医学-危重病医学

CiteScore

51.50

自引率

2.80%

发文量

326

审稿时长

1 months

期刊介绍： Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.