Grunow, Julius J; Reiher, Katja; Carbon, Niklas M; Engelhardt, Lilian Jo; Mai, Knut; Koch, Susanne; Schefold, Joerg C; Z'Graggen, Werner; Schaller, Stefan J; Fielitz, Jens; Spranger, Joachim; Weber-Carstens, Steffen; Wollersheim, Tobias (2022). Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients. Critical care, 26(1), p. 237. BioMed Central 10.1186/s13054-022-04101-1
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BACKGROUND
The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition.
METHODS
A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated.
RESULTS
MSTN gene expression (median [IQR] fold change: 1.00 [0.68-1.54] vs. 0.26 [0.11-0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p < 0.001). Patients with ICUAW versus without ICUAW showed significantly lower MSTN gene expression levels (median [IQR] fold change: 0.17 [0.10/0.33] and 0.51 [0.20/0.86]; p = 0.047). Myostatin levels were directly correlated with muscle strength (correlation coefficient 0.339; p = 0.020) and insulin sensitivity index (correlation coefficient 0.357; p = 0.015). No association was observed between myostatin plasma concentrations as well as MSTN expression levels and levels of mobilization, electrophysiological variables, or markers of atrophy pathways.
CONCLUSION
Muscular gene expression and systemic protein levels of myostatin are downregulated during critical illness. The previously proposed therapeutic inhibition of myostatin does therefore not seem to have a pathophysiological rationale to improve muscle quality in critically ill patients.
TRIAL REGISTRATION
ISRCTN77569430 -13th of February 2008 and ISRCTN19392591 17th of February 2011.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery 04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology 04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care |
UniBE Contributor: |
Schefold, Jörg Christian, Z'Graggen, Werner Josef |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1364-8535 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
05 Aug 2022 10:52 |
Last Modified: |
05 Dec 2022 16:22 |
Publisher DOI: |
10.1186/s13054-022-04101-1 |
PubMed ID: |
35922829 |
Uncontrolled Keywords: |
Critical illness ICUAW Insulin resistance Muscle atrophy Myostatin |
BORIS DOI: |
10.48350/171768 |
URI: |
https://boris.unibe.ch/id/eprint/171768 |
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