Muscle wasting and impaired muscle oxidative metabolism are common extrapulmonary features of chronic respiratory failure (CRF) that significantly increase disease burden. This review aims to address the question whether hypoxia, an obvious consequence of this disease, actually plays a causal role in these muscle impairments.
In experimental models, a causal role for hypoxia in muscle atrophy and metabolic impairments has clearly been shown. Although the hypoxia-inducible factors and nuclear factor kappa B are putative mediators of these hypoxia-induced alterations, their true involvement remains to be proven. Molecular signatures of disrupted regulation of muscle mass and oxidative metabolism observed in these experimental models also have been shown in muscles of patients suffering from CRF, suggestive of but not conclusive for a causal role of hypoxia. Therapies, including but not restricted to those aimed at alleviating hypoxia, have been shown to partially but not completely restore muscle mass and oxidative capacity in CRF patients, which may imply an additive effect of nutritional modulation of substrate metabolism.
Although hypoxia clearly affects skeletal muscle maintenance, it remains to be confirmed whether and by which underlying molecular mechanisms hypoxia is causally involved in CRF-related muscle atrophy and impaired oxidative capacity.
aNutrim School for Nutrition, Toxicology and Metabolism, Department of Anatomy and Embryology, Maastricht University Medical Centre+, Maastricht, The Netherlands
bService de Physiologie Clinique et de l’Exercice, Hôpital Nord, CHU Saint-Etienne
cLaboratoire Physiologie de l’Exercice, EA4338 Université Jean Monnet, Saint-Etienne, France
dNutrim School for Nutrition, Toxicology and Metabolism, Department of Anatomy and Embryology, Maastricht University Medical Centre+, Maastricht, The Netherlands
eClinique de Pneumologie, CHU Grenoble
fUniversité Joseph Fourier
hEuropean Institute for Systems Biology & Medicine, Lyon, France
Correspondence to H.R. Gosker, Department of Respiratory Medicine, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands Tel: +31 43 3884247; e-mail: email@example.com