BACKGROUND: A significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation, which correlate with increased mortality. AIM: To determine the molecular mechanisms mediating decreased capillary formation in COPD. METHODS: 24 patients with COPD and 12 matching controls were recruited. Patients with COPD were classified into mild, moderate and severe groups according to GOLD (global initiative for chronic obstructive lung disease) criteria. Biopsy specimens were obtained from the tibialis anterior muscle. Fibre typing and capillary formation, together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF1alpha and HIF3alpha), vascular endothelial growth factors (VEGF-A, VEGF-B and VEGF-C isoforms) and von Hippel-Lindau (VHL) protein, were determined. VHL expression and localisation were further studied by immunohistochemistry. RESULTS: Skeletal muscle capillary formation decreased significantly with increasing disease severity. Compared with controls, a tendency to mRNA overexpression of HIF1alpha, HIF3alpha and VEGF isoforms was observed in mild and moderate COPD, which decreased at the severe stage. In contrast, skeletal muscle biopsy samples from patients with COPD exhibited significant overexpression of VHL at both the mRNA and protein level by immunohistochemistry. VHL protein was further determined to be localised to satellite cells. CONCLUSIONS: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may have a negative effect on transduction of the hypoxic signal and may contribute to decreased capillarisation in skeletal muscles of patients with COPD.
BACKGROUND: A significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation, which correlate with increased mortality. AIM: To determine the molecular mechanisms mediating decreased capillary formation in COPD. METHODS: 24 patients with COPD and 12 matching controls were recruited. Patients with COPD were classified into mild, moderate and severe groups according to GOLD (global initiative for chronic obstructive lung disease) criteria. Biopsy specimens were obtained from the tibialis anterior muscle. Fibre typing and capillary formation, together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF1alpha and HIF3alpha), vascular endothelial growth factors (VEGF-A, VEGF-B and VEGF-C isoforms) and von Hippel-Lindau (VHL) protein, were determined. VHL expression and localisation were further studied by immunohistochemistry. RESULTS: Skeletal muscle capillary formation decreased significantly with increasing disease severity. Compared with controls, a tendency to mRNA overexpression of HIF1alpha, HIF3alpha and VEGF isoforms was observed in mild and moderate COPD, which decreased at the severe stage. In contrast, skeletal muscle biopsy samples from patients with COPD exhibited significant overexpression of VHL at both the mRNA and protein level by immunohistochemistry. VHL protein was further determined to be localised to satellite cells. CONCLUSIONS: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may have a negative effect on transduction of the hypoxic signal and may contribute to decreased capillarisation in skeletal muscles of patients with COPD.
Authors: Qiyuan Zhou; Tianji Chen; Wei Zhang; Melike Bozkanat; Yongchao Li; Lei Xiao; Richard B van Breemen; John W Christman; Jacob I Sznajder; Guofei Zhou Journal: Am J Respir Cell Mol Biol Date: 2016-05 Impact factor: 6.914
Authors: Qiyuan Zhou; Annie Pardo; Melanie Königshoff; Oliver Eickelberg; G R Scott Budinger; Krishna Thavarajah; Cara J Gottardi; Jonathan Jones; John Varga; Moises Selman; Jacob I Sznajder; J Usha Raj; Guofei Zhou Journal: FASEB J Date: 2011-06-03 Impact factor: 5.191
Authors: François Maltais; Marc Decramer; Richard Casaburi; Esther Barreiro; Yan Burelle; Richard Debigaré; P N Richard Dekhuijzen; Frits Franssen; Ghislaine Gayan-Ramirez; Joaquim Gea; Harry R Gosker; Rik Gosselink; Maurice Hayot; Sabah N A Hussain; Wim Janssens; Micheal I Polkey; Josep Roca; Didier Saey; Annemie M W J Schols; Martijn A Spruit; Michael Steiner; Tanja Taivassalo; Thierry Troosters; Ioannis Vogiatzis; Peter D Wagner Journal: Am J Respir Crit Care Med Date: 2014-05-01 Impact factor: 21.405
Authors: Nil Turan; Susana Kalko; Anna Stincone; Kim Clarke; Ayesha Sabah; Katherine Howlett; S John Curnow; Diego A Rodriguez; Marta Cascante; Laura O'Neill; Stuart Egginton; Josep Roca; Francesco Falciani Journal: PLoS Comput Biol Date: 2011-09-01 Impact factor: 4.475