Dataset Information

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, 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.

SUBMITTER: Tenyi A

PROVIDER: S-EPMC5819708 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Tényi Ákos Á Cano Isaac I Marabita Francesco F Kiani Narsis N Kalko Susana G SG Barreiro Esther E de Atauri Pedro P Cascante Marta M Gomez-Cabrero David D Roca Josep J

Journal of translational medicine 20180220 1

<h4>Background</h4>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.<h4>Methods</ ...[more]

PMID: 29463285

Similar Datasets

Project description:BackgroundSkeletal muscle impairment is a recognized complication of COPD, predicting mortality in severe disease. Increasing evidence implicates the renin-angiotensin system in control of muscle phenotype. We hypothesized that angiotensin-converting enzyme (ACE) inhibition would improve quadriceps function and exercise performance in COPD.MethodsThis double-blind, randomized placebo-controlled trial investigated the effect of the ACE inhibitor, fosinopril, on quadriceps function in patients with COPD with quadriceps weakness. Primary outcomes were change in quadriceps endurance and atrophy signaling at 3 months. Quadriceps maximum voluntary contraction (QMVC), mid-thigh CT scan of the cross-sectional area (MTCSA), and incremental shuttle walk distance (ISWD) were secondary outcomes.ResultsEighty patients were enrolled (mean [SD], 65 [8] years, FEV1 43% [21%] predicted, 53% men). Sixty-seven patients (31 fosinopril, 36 placebo) completed the trial. The treatment group demonstrated a significant reduction in systolic BP (?-10.5 mm Hg; 95% CI, -19.9 to -1.1; P = .03) and serum ACE activity (?-20.4 IU/L; 95% CI, -31.0 to -9.8; P < .001) compared with placebo. No significant between-group differences were observed in the primary end points of quadriceps endurance half-time (?0.5 s; 95% CI, -13.3-14.3; P = .94) or atrogin-1 messenger RNA expression (?-0.03 arbitrary units; 95% CI, -0.32-0.26; P = .84). QMVC improved in both groups (fosinopril: ?1.1 kg; 95% CI, 0.03-2.2; P = .045 vs placebo: ?3.6 kg; 95% CI, 2.1-5.0; P < .0001) with a greater increase in the placebo arm (between-group, P = .009). No change was shown in the MTCSA (P = .09) or ISWD (P = .51).ConclusionsThis randomized controlled trial found that ACE inhibition, using fosinopril for 3 months, did not improve quadriceps function or exercise performance in patients with COPD with quadriceps weakness.Trial registryCurrent Controlled Trials; No.: ISRCTN05581879; URL: www.controlled-trials.com.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets