ORIGINAL ARTICLES

Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease

K Jatta¹, G Eliason¹, G M Portela-Gomes², L Grimelius², O Caro³, L Nilholm³, A Sirjsö¹, K Piehl-Aulin¹ and S M Abdel-Halim^1,3

¹ Department of Clinical Medicine, Örebro University, Sweden
² Department of Genetics and Pathology, Uppsala University, Sweden
³ Department of Respiratory Medicine, Örebro University Hospital, Örebro, Sweden

Correspondence to:
Dr S Abdel-Halim, Department of Respiratory Medicine, Örebro University Hospital, 701 85 Örebro, Sweden; samy.halim{at}gmail.com

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 (HIF1 and HIF3), 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 HIF1, HIF3 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.

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