Author(s): PEÑAILILLO, L., BONICIOLI, J., CAMPOS-ACEVEDO, C., GUTIÉRREZ, S., CIFUENTES-SILVA, E., PORTAL-RODRÍGUEZ, M., FONCEA, M., MÉNDEZ, A., HENRÍQUEZ, M., HENRÍQUEZ, J.P., CABELLO-VERRUGIO, C., Institution: UNIVERSIDAD ANDRES BELLO, Country: CHILE, Abstract-ID: 1613

INTRODUCTION:
Chronic obstructive pulmonary disease (COPD) is most frequently induced by cigarette smoking (CS) and is a leading cause of death. COPD also induces muscle dysfunction (1). The mechanisms for muscle dysfunction include a decrease in muscle oxidative capacity, decreased muscle protein synthesis, and increased degradation. Animal models (i.e., mice) of COPD have investigated primarily pulmonary manifestations of CS. Thus, few studies have investigated the effects of CS on skeletal muscle in mice. Aim: To compare muscle oxidative capacity, decreased muscle protein synthesis, and increased degradation between mice with CS-induced COPD and control animals.
METHODS:
Twenty 10-week-old, female, A/J mice were assigned to a control (room air; CTRL) or COPD group (CS exposure: 24 weeks, 5 days/week). Body mass, grip strength, aerobic capacity, and voluntary movement were assessed every 8 weeks. After exposure, mice were euthanized, and lung and muscle tissues were analyzed. Alveolar diameter was determined from lung tissue as a marker of emphysema. Tibialis anterior (TA), soleus (SOL), and gastrocnemius (GA) muscle proteins, muscle fiber cross-sectional area, relative gene expression, and neuromuscular junction (NMJ) morphology were assessed.
RESULTS:
COPD mice had 12.2% greater alveolar diameter than CTRL (p<0.05). Grip strength decreased by 18% after 24 weeks of CS (P=0.01), but aerobic capacity and voluntary movement remained unchanged. Muscle mass was similar between groups. GA muscle in COPD mice had 243% higher p70s6K protein levels (P=0.003) than CTRL, while no other differences in total protein content were observed in individual muscles. Pooled muscle analysis showed an increased level of NLP3 (+87%, P=0.04) and COX-IV (+87%, P=0.003). Mitochondrial Complexes II (-73.6%; P=0.0009) and IV (-38.4%; P=0.01) were reduced in COPD when normalized to COX-IV. In distal lumbrical muscles, NMJs exhibit increased postsynaptic fragmentation and density of acetylcholine receptors (AChRs).
CONCLUSION:
CS exposure induced mild emphysema, decreased muscle strength, mitochondrial dysfunction, increased inflammatory signaling, and signs of synaptic adaptive changes at the NMJ, suggesting compensatory responses to temporal hypoxia and pulmonary inflammation/damage.