Abstract
Background 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) compared to those without wasting (non-atrophic patients with COPD). Extracellular matrix (ECM) proteins are major constituents of the cell microenvironment steering cell behaviour and regeneration. We investigated whether the composition of ECM in atrophic compared non-atrophic patients with COPD differs in response to PR.
Methods Vastus lateralis muscle biopsies from 29 male COPD patients (mean±sem FEV1: 43±6% predicted) classified according to their fat-free mass index as atrophic (<17 kg.m−2, n=10) or non-atrophic (≥17 kg.m−2, n=19) were analysed before and after a 10-week PR programme for myofiber distribution and size, whereas a selection of ECM molecules was quantified using ELISA and Realtime-PCR.
Results In non-atrophic patients with COPD PR was associated with increased myofiber 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 myofiber 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 non-atrophic 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 non-atrophic 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 up-regulated 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 myofiber adaptations in atrophic compared to non-atrophic patients with COPD could be associated with inadequate remodelling of the intramuscular ECM environment.
Footnotes
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Conflict of interests: The authors declare no competing financial interests. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- Received May 27, 2024.
- Accepted July 31, 2024.
- Copyright ©The authors 2024.
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