Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients
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Published:2022-08-03
Issue:1
Volume:26
Page:
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ISSN:1364-8535
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Container-title:Critical Care
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language:en
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Short-container-title:Crit Care
Author:
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 SteffenORCID, Wollersheim Tobias
Abstract
Abstract
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.
Graphical abstract
Funder
Berlin Institute of Health Deutsche Forschungsgemeinschaft Deutsches Zentrum für Herz-Kreislaufforschung Charité - Universitätsmedizin Berlin
Publisher
Springer Science and Business Media LLC
Subject
Critical Care and Intensive Care Medicine
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