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Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819708/ https://www.ncbi.nlm.nih.gov/pubmed/29463285 http://dx.doi.org/10.1186/s12967-018-1405-y |
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author | Tényi, Ákos Cano, Isaac Marabita, Francesco Kiani, Narsis Kalko, Susana G. Barreiro, Esther de Atauri, Pedro Cascante, Marta Gomez-Cabrero, David Roca, Josep |
author_facet | Tényi, Ákos Cano, Isaac Marabita, Francesco Kiani, Narsis Kalko, Susana G. Barreiro, Esther de Atauri, Pedro Cascante, Marta Gomez-Cabrero, David Roca, Josep |
author_sort | Tényi, Ákos |
collection | PubMed |
description | 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, FEV(1) 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 (VO(2) peak, Watts peak, BODE index and blood lactate levels) (P < 0.05 each), but not with lung function (FEV(1)). 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1405-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5819708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58197082018-02-26 Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients Tényi, Ákos Cano, Isaac Marabita, Francesco Kiani, Narsis Kalko, Susana G. Barreiro, Esther de Atauri, Pedro Cascante, Marta Gomez-Cabrero, David Roca, Josep J Transl Med Research 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, FEV(1) 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 (VO(2) peak, Watts peak, BODE index and blood lactate levels) (P < 0.05 each), but not with lung function (FEV(1)). 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1405-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-20 /pmc/articles/PMC5819708/ /pubmed/29463285 http://dx.doi.org/10.1186/s12967-018-1405-y Text en © 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. |
spellingShingle | Research Tényi, Ákos Cano, Isaac Marabita, Francesco Kiani, Narsis Kalko, Susana G. Barreiro, Esther de Atauri, Pedro Cascante, Marta Gomez-Cabrero, David Roca, Josep Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients |
title | Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients |
title_full | Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients |
title_fullStr | Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients |
title_full_unstemmed | Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients |
title_short | Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients |
title_sort | network modules uncover mechanisms of skeletal muscle dysfunction in copd patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819708/ https://www.ncbi.nlm.nih.gov/pubmed/29463285 http://dx.doi.org/10.1186/s12967-018-1405-y |
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