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

Uzun Ayar C, Güiza F, Derese I, Pauwels L, Vander Perre S, Pintelon I, Casaer M, Van Aerde N, Hermans G, Derde S, Kreiß L, Van den Berghe G, Vanhorebeek I (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Intensive Care Medicine

DOI: 10.1007/s00134-025-07949-3

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.

Authors with CRIS profile

Lucas Kreiß Lehrstuhl für Medizinische Biotechnologie (MBT)

Involved external institutions

Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) University of Antwerp / Universiteit Antwerpen BE Belgium (BE)

How to cite

APA:

Uzun Ayar, C., Güiza, F., Derese, I., Pauwels, L., Vander Perre, S., Pintelon, I.,... Vanhorebeek, I. (2025). Altered muscle transcriptome as molecular basis of long-term muscle weakness in survivors from critical illness. Intensive Care Medicine. https://doi.org/10.1007/s00134-025-07949-3

MLA:

Uzun Ayar, Ceren, et al. "Altered muscle transcriptome as molecular basis of long-term muscle weakness in survivors from critical illness." Intensive Care Medicine (2025).

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