S131 The effect of pulmonary rehabilitation on extracellular matrix protein expression in vastus lateralis muscle in atrophic and non-atrophic patients with COPD

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Background In response to exercise-based pulmonary rehabilitation (PR), the type of muscle fibre remodelling differs between COPD with peripheral muscle wasting (atrophic COPD) compared to those without wasting (non-atrophic COPD). Extracellular matrix (ECM) proteins are major constituents of the cell microenvironment steering cell behaviour and regeneration. We recently showed that the baseline differences in mRNA expression for several ECM molecules between atrophic and not atrophic COPD are not translated at the protein level. We interpreted this finding as an indication of an accumulation of long-lived ECM proteins and dysregulated proteostasis as it is commonly seen during deconditioning and ageing. Aim To investigate whether differences in the ECM profile between atrophic and non-atrophic COPD can be modified in response to PR. Methods Vastus lateralis muscle biopsies from 29 COPD patients (FEV1: 55±12% 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 exercise-based PR programme for myofiber distribution and size, whereas a selection of ECM molecules was quantified using ELISA and Realtime-PCR. Results PR was associated with increased myofiber type I distribution and hypertrophy in non-atrophic COPD and with increased myofiber type IIa distribution and hypertrophy in atrophic COPD. PR induced diverse intramuscular ECM adaptations in atrophic compared to non-atrophic COPD. Accordingly, mRNA and protein levels of expression of ECM biomarkers (collagen type I and IV, and decorin) were significantly increased following PR only in non-atrophic COPD (figures 1a, 1b and 1c, respectively). Conversely, post-PR, osteopontin, a protein known for its dystrophic effects (figure 1d), and tenacin C, a necroptosis compensatory factor facilitating muscle regeneration (figure 1e), were upregulated at both mRNA and protein levels only in atrophic COPD, whereas fibronectin protein levels were decreased (figure 1f) in atrophic COPD. Conclusions These findings suggest that the differential PR-induced myofiber adaptations in atrophic compared to non-atrophic COPD could be associated with inadequate remodelling of the intramuscular ECM environment. Furthermore, rehabilitation-induced diverse ECM protein adaptation in atrophic compared to non-atrophic COPD highlights novel mechanisms for myofiber atrophy. Identification of atrophy-specific ECM proteins can offer new treatments.

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