Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients
Julius J. Grunow,
Katja Reiher,
Niklas M. Carbon,
Lilian Jo Engelhardt,
Knut Mai,
Susanne Koch,
Joerg C. Schefold,
Werner Z’Graggen,
Stefan J. Schaller,
Jens Fielitz,
Joachim Spranger,
Steffen Weber-Carstens,
Tobias Wollersheim
Affiliations
Julius J. Grunow
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Katja Reiher
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Niklas M. Carbon
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Lilian Jo Engelhardt
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Knut Mai
Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin
Susanne Koch
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Joerg C. Schefold
Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University Bern
Werner Z’Graggen
Departments of Neurology and Neurosurgery, Inselspital, Bern University Hospital, University Bern
Stefan J. Schaller
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Jens Fielitz
Charité – Universitätsmedizin Berlin, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center (ECRC)
Joachim Spranger
Department of Endocrinology and Metabolic Diseases, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin
Steffen Weber-Carstens
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Tobias Wollersheim
Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
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
