Role of pulmonary rehabilitation in extracellular matrix protein expression in vastus lateralis muscle in atrophic and nonatrophic patients with COPD

In response to exercise-based pulmonary rehabilitation (PR), the type of muscle fibre remodelling differs between COPD patients with peripheral muscle wasting (atrophic patients with COPD) and those without wasting (nonatrophic patients with COPD). Extracellular matrix (ECM) proteins are major constituents of the cell micro-environment steering cell behaviour and regeneration. We investigated whether the composition of ECM in atrophic compared to nonatrophic patients with COPD differs in response to PR.

These findings suggest that the differential PR-induced myofibre adaptations in atrophic compared to nonatrophic patients with COPD could be associated with inadequate remodelling of the intramuscular ECM environment.

Vastus lateralis muscle biopsies from 29 male COPD patients (mean±sem forced expiratory volume in 1 s: 43±6% predicted) classified according to their fat-free mass index as atrophic (<17 kg·m-2, n=10) or nonatrophic (≥17 kg·m-2, n=19) were analysed before and after a 10-week PR programme for myofibre distribution and size, whereas a selection of ECM molecules was quantified using ELISA and real-time PCR.

In nonatrophic patients with COPD PR was associated with increased myofibre type I distribution (by 6.6±2.3%) and cross-sectional area (CSA) (by 16.4±4.8%), whereas in atrophic patients with COPD, PR induced increased myofibre type IIa distribution (by 9.6±2.8%) and CSA (by 12.1±3.2%). PR induced diverse intramuscular ECM adaptations in atrophic compared to nonatrophic patients with COPD. Accordingly, following PR there was a significant increase in protein levels of ECM biomarkers (collagen type I by 90 pg·mL-1; collagen type IV by 120 pg·mL-1; decorin by 70 pg·mL-1) only in nonatrophic patients with COPD. Conversely, post-PR, osteopontin, a protein known for its dystrophic effects, and tenacin C, a necroptosis compensatory factor facilitating muscle regeneration, were upregulated at protein levels (by 280 pg·mL-1and 40 pg·mL-1, respectively) in atrophic patients with COPD, whereas fibronectin protein levels were decreased. Conclusions: These findings suggest that the differential PR-induced myofibre adaptations in atrophic compared to nonatrophic patients with COPD could be associated with inadequate remodelling of the intramuscular ECM environment.