Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients
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, pote...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-018-1405-y |
| _version_ | 1818994888993144832 |
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| author | Ákos Tényi Isaac Cano Francesco Marabita Narsis Kiani Susana G. Kalko Esther Barreiro Pedro de Atauri Marta Cascante David Gomez-Cabrero Josep Roca |
| author_facet | Ákos Tényi Isaac Cano Francesco Marabita Narsis Kiani Susana G. Kalko Esther Barreiro Pedro de Atauri Marta Cascante David Gomez-Cabrero Josep Roca |
| author_sort | Ákos Tényi |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-20T21:05:07Z |
| format | Article |
| id | doaj.art-89843fee14ad480fb516875b3bcd3a8e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-20T21:05:07Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-89843fee14ad480fb516875b3bcd3a8e2022-12-21T19:26:38ZengBMCJournal of Translational Medicine1479-58762018-02-0116111210.1186/s12967-018-1405-yNetwork modules uncover mechanisms of skeletal muscle dysfunction in COPD patientsÁkos Tényi0Isaac Cano1Francesco Marabita2Narsis Kiani3Susana G. Kalko4Esther Barreiro5Pedro de Atauri6Marta Cascante7David Gomez-Cabrero8Josep Roca9Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaHospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaUnit of Computational Medicine, Department of Medicine, Karolinska InstituteUnit of Computational Medicine, Department of Medicine, Karolinska InstituteHospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaCenter for Biomedical Network Research in Respiratory Diseases (CIBERES)Departament de Bioquimica i Biologia Molecular, Facultat de Biologia-IBUB, Universitat de BarcelonaDepartament de Bioquimica i Biologia Molecular, Facultat de Biologia-IBUB, Universitat de BarcelonaUnit of Computational Medicine, Department of Medicine, Karolinska InstituteHospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de BarcelonaAbstract 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: NCT03169270http://link.springer.com/article/10.1186/s12967-018-1405-yGene modulesChronic obstructive pulmonary diseaseExercise trainingSystems medicineMuscular weakness |
| spellingShingle | Ákos Tényi Isaac Cano Francesco Marabita Narsis Kiani Susana G. Kalko Esther Barreiro Pedro de Atauri Marta Cascante David Gomez-Cabrero Josep Roca Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients Journal of Translational Medicine Gene modules Chronic obstructive pulmonary disease Exercise training Systems medicine Muscular weakness |
| 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 | Gene modules Chronic obstructive pulmonary disease Exercise training Systems medicine Muscular weakness |
| url | http://link.springer.com/article/10.1186/s12967-018-1405-y |
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