Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients

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• dc.contributor.author Tényi, Ákos
• dc.contributor.author Cano, Isaac
• dc.contributor.author Marabita, Francesco
• dc.contributor.author Kiani, Narsis A.
• dc.contributor.author Kalko, Susana G.
• dc.date.accessioned 2018-11-28T08:40:00Z
• dc.date.available 2018-11-28T08:40:00Z
• dc.date.issued 2018
• dc.description.abstract BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients often show skeletal muscle dysfunction that has a prominent negative impact on prognosis. The study aims to further explore underlying mechanisms of skeletal muscle dysfunction as a characteristic systemic effect of COPD, potentially modifiable with preventive interventions (i.e. muscle training). The research analyzes network module associated pathways and evaluates the findings using independent measurements. METHODS: We characterized the transcriptionally active network modules of interacting proteins in the vastus lateralis of COPD patients (n = 15, FEV1 46 ± 12% pred, age 68 ± 7 years) and healthy sedentary controls (n = 12, age 65 ± 9 years), at rest and after an 8-week endurance training program. Network modules were functionally evaluated using experimental data derived from the same study groups. RESULTS: At baseline, we identified four COPD specific network modules indicating abnormalities in creatinine metabolism, calcium homeostasis, oxidative stress and inflammatory responses, showing statistically significant associations with exercise capacity (VO2 peak, Watts peak, BODE index and blood lactate levels) (P < 0.05 each), but not with lung function (FEV1). Training-induced network modules displayed marked differences between COPD and controls. Healthy subjects specific training adaptations were significantly associated with cell bioenergetics (P < 0.05) which, in turn, showed strong relationships with training-induced plasma metabolomic changes; whereas, effects of training in COPD were constrained to muscle remodeling. CONCLUSION: In summary, altered muscle bioenergetics appears as the most striking finding, potentially driving other abnormal skeletal muscle responses. Trial registration The study was based on a retrospectively registered trial (May 2017), ClinicalTrials.gov identifier: NCT03169270.
• dc.description.sponsorship We want to acknowledge the support of the European Commission (FP7)grants SYNERGY-COPD (no. FP7-ICT-2009-270086), the AGAUR (2009SGR911 and 2014SGR1017), CERCA Programme / Generalitat de Catalunya (2014SGR661) and The ’ICREA Academia’ prize for excellence in research, ICREA foundation-Generalitat de Catalunya (to M.C.).
• dc.format.mimetype application/pdf
• dc.identifier.citation Tényi Á, Cano I, Marabita F, Kiani N, Kalko SG7, Barreiro E et al. Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients. J Transl Med. 2018 Feb 20;16(1):34. DOI: 10.1186/s12967-018-1405-y
• dc.identifier.doi http://dx.doi.org/10.1186/s12967-018-1405-y
• dc.identifier.issn 1479-5876
• dc.identifier.uri http://hdl.handle.net/10230/35870
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Journal of Translational Medicine. 2018 Feb 20;16(1):34
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/689802
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/270086
• dc.rights © The Author(s) 2018. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Chronic obstructive pulmonary disease
• dc.subject.keyword Exercise training
• dc.subject.keyword Gene modules
• dc.subject.keyword Muscular weakness
• dc.subject.keyword Systems medicine
• dc.subject.other Pulmons -- Malalties obstructives
• dc.title Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion