Year: 2018
Type: article
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, FEV146 ± 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 (VO2peak, 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 registrationThe study was based on a retrospectively registered trial (May 2017), ClinicalTrials.gov identifier: NCT03169270
Institutions: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Karolinska Institutet, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Municipal Institute for Medical Research, Hospital del Mar Research Institute, Institut de Biomedicina de la Universitat de Barcelona, King's College London
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: Centres de Recerca de Catalunya, European Commission, Generalitat de Catalunya, Institució Catalana de Recerca i Estudis Avançats, Horizon 2020 Framework Programme, Agència de Gestió d'Ajuts Universitaris i de Recerca, H2020 Societal Challenges, FP7 Information and Communication Technologies
Awards: G2063481571, G2203972493, G2896455309, G3281641236, G4916640921, G4937468798, G5277875382, G600682980, G6127711652, G6582448267, G7248275097, Personalised Connected Care for Complex Chronic Patients, Modelling and simulation environment for systems medicine\n(Chronic obstructive pulmonary disease -COPD- as a use case)
OpenAlex ID: W2796186950