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Title: Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients
Author: Tényi, Ákos
Cano Franco, Isaac
Marabita, Francesco
Kiani, Narsis A.
Kalko, Susana
Barreiro, Esther
Atauri Carulla, Ramón de
Cascante i Serratosa, Marta
Gomez Cabrero, David
Roca Torrent, Josep
Keywords: Malalties pulmonars obstructives cròniques
Expressió gènica
Malalties musculars
Chronic obstructive pulmonary diseases
Gene expression
Muscular Diseases
Issue Date: 20-Feb-2018
Publisher: BioMed Central
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), identifier: NCT03169270.
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It is part of: Journal of Translational Medicine, 2018, vol. 16, num. 1, p. 34
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ISSN: 1479-5876
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Medicina)

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