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Overexpression of von Hippel-Lindau protein in skeletal muscles of patients with chronic obstructive pulmonary disease
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
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2009 (English)In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 62, no 1, p. 70-76Article in journal (Refereed) Published
Abstract [en]

Background/aim: A Significant number of patients with chronic obstructive pulmonary disease (COPD) exhibit skeletal muscle wasting and decreased capillary area formation which have been correlated to increased mortality. The current study aimed to determine the molecular mechanisms mediating decreased capillary formation in COPD.

Methods: Twenty-four COPD patients and twelve matching controls were recruited. COPD patients were divided into mild, moderate and severe groups according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. Skeletal muscle biopsies were obtained from the tibialis anterior muscle. Fibre typing and capillary formation together with messenger RNA (mRNA) expression of hypoxia-inducible factors (HIF-1á and HIF-3á ), vascular endothelial growth factors (VEGF-A, -B and -C isoforms) and von Hippel Lindau (VHL) were determined. VHL expression and localization was further studied by immunohistochemistry.

Results: Skeletal muscle capillary formation was significantly decreased with ascending disease severity. Compared to controls, a tendency to mRNA overexpression of HIF-1á, HIF-3á and VEGF isoforms was observed at mild and moderate COPD that decreased at the severe stage. By contrast, skeletal muscle biopsies from COPD patients exhibited significant overexpression of VHL both on the mRNA and protein levels by immunohistochemistry. VHL protein was further determined to be localized to satellite cells.

Conclusions: Overexpression of VHL was identified in the skeletal muscle of patients with COPD. Increased VHL activity may exert a negative impact on transducing the hypoxic signal and may contribute to decreased capillarization in skeletal muscles of patients with COPD.

Place, publisher, year, edition, pages
London: BMJ Publishing Group Ltd, 2009. Vol. 62, no 1, p. 70-76
National Category
Medical and Health Sciences Cell and Molecular Biology
Research subject
Pathology; Medicine
Identifiers
URN: urn:nbn:se:oru:diva-3418DOI: 10.1136/jcp.2008.057190ISI: 000262420400018PubMedID: 18818266Scopus ID: 2-s2.0-58349102711OAI: oai:DiVA.org:oru-3418DiVA, id: diva2:137715
Available from: 2008-12-04 Created: 2008-12-04 Last updated: 2018-01-13Bibliographically approved
In thesis
1. Sceletal muscle characteristics and physical activity patterns in COPD
Open this publication in new window or tab >>Sceletal muscle characteristics and physical activity patterns in COPD
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Besides abnormities within the respiratory system COPD is also associated with effects outside the lungs, so called systemic effects. One systemic effect that has been highlighted is skeletal muscle dysfunction which has also been associated with reduced exercise capacity. Apart from changes in muscle morphology, low levels of physical activity have also been suggested as a plausible mediator of reduced exercise capacity in COPD. The aim of this thesis was to study muscle morphology and physical activity patterns in patients with different degrees of COPD and to examine the associations between muscle morphology, physical activity and exercise capacity in these patients. Skeletal muscle morphology was found to shift towards a more glycolytic muscle profile in COPD patients and changes in muscle morphology were found to be correlated to disease severity and to exercise capacity. Muscle capillarization was also found to be lower in COPD compared with healthy subjects and to be correlated to disease severity and exercise capacity. When studying signalling pathways involved in muscle capillarization, an overexpression of VHL was found in patients with mild and moderate COPD compared with healthy subjects. Furthermore, COPD patients were found to be less physically active compared with healthy subjects and the level of physical activity was associated with exercise capacity.In conclusion, changes in skeletal muscle morphology and low levels of physical activity are present in COPD patients and may partly explain the lower exercise capacity observed in these patients. The more glycolytic muscle profile in COPD is suggested to be mediated by hypoxia and low levels of physical activity in this patient group. Furthermore, increased levels of VHL may lead to impaired transduction of the hypoxic signalling pathway, which may contribute to the decreased muscle capillarization observed in COPD.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2010. p. 65
Series
Örebro Studies in Sport Sciences, ISSN 1654-7535 ; 10
Keyword
COPD, muscle morphology, muscle fibre distribution, muscle capillarization, physical activity, von Hippel-Lindau protein, exercise capacity
National Category
Social Sciences Interdisciplinary Sport and Fitness Sciences
Research subject
Sports Science
Identifiers
urn:nbn:se:oru:diva-12341 (URN)978-91-7668-768-0 (ISBN)
Public defence
2011-01-14, Hörsal P2, Fakutetsgatan 1, Örebro universitet, Örebro, 13:00
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Available from: 2010-10-27 Created: 2010-10-27 Last updated: 2018-01-12Bibliographically approved

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Jatta, KenEliason, GabriellaSirsjö, AllanPiehl-Aulin, KarinAbdel-Halim, Samy M.

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