Abstract

Exercise training (ET) for Chronic Obstructive Pulmonary Disease (COPD) patients has limited beneficial effects on peripheral muscles. A deleterious systemic microenvironment of the muscle cells, coming from the spillover of inflammatory molecules from the lungs into the systemic circulation (Barnes and Celli, ERJ 2009), could be a cause of these limited effects.

Our objective was to assess the role of the COPD serum in the limited response of COPD muscles to ET using an in vitro approach of cultured human myotubes.

Myotubes from 8 healthy subjects were cultured in presence of a pool of 6 healthy serums (FEV1%: 103.0% [89.5-127.3]) or 6 COPD serums (FEV1%: 33.5% [26.7-48.5]; BODE: 4.5 [4-6]) obtained before and after ET. We compared the variations of inflammation, oxidative stress and atrophy markers in the myotubes exposed to healthy post-ET vs pre-ET serum (healthy ET condition), and COPD post-ET vs pre-ET serum (COPD ET condition). We then compared the effects observed in the healthy ET condition to those in the COPD ET condition.

Expression of degradation markers were increased in myotubes exposed to COPD ET condition compared to healthy ET condition (myostatin +78% vs -3%; MuRF1 +38% vs -2%; AMBRA1 +15% vs -3%; p<0.05), while the myotube diameter was reduced in COPD ET condition (-12% vs +20%; p<0.05). No difference was observed for inflammation and oxidative stress markers.

We show that post-ET serum from COPD patients induces atrophy of healthy human myotubes through increased expression of degradation markers. These results suggest that a deleterious systemic microenvironment of the COPD muscle could contribute to explain the limited effects of ET in COPD patients.