Format

Send to

Choose Destination
J Transl Med. 2018 Feb 20;16(1):34. doi: 10.1186/s12967-018-1405-y.

Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients.

Author information

1
Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain. tenyi@clinic.cat.
2
Center for Biomedical Network Research in Respiratory Diseases (CIBERES), Madrid, Spain. tenyi@clinic.cat.
3
Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
4
Center for Biomedical Network Research in Respiratory Diseases (CIBERES), Madrid, Spain.
5
Unit of Computational Medicine, Department of Medicine, Karolinska Institute, 171 77, Stockholm, Sweden.
6
Center for Molecular Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
7
Bioinformatics Core Facility, IDIBAPS-CEK, Hospital Clínic, University de Barcelona, Barcelona, Spain.
8
Pulmonology Dept, Muscle and Respiratory System Research Unit, IMIM-Hospital del Mar, Universitat Pompeu Fabra, PRBB, Barcelona, Spain.
9
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia-IBUB, Universitat de Barcelona, 08028, Barcelona, Spain.
10
Mucosal and Salivary Biology Division, King's College London Dental Institute, London, SE1 9RT, UK.
11
Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain. jroca@clinic.cat.
12
Center for Biomedical Network Research in Respiratory Diseases (CIBERES), Madrid, Spain. jroca@clinic.cat.

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.

KEYWORDS:

Chronic obstructive pulmonary disease; Exercise training; Gene modules; Muscular weakness; Systems medicine

PMID:
29463285
PMCID:
PMC5819708
DOI:
10.1186/s12967-018-1405-y
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center