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First published online October 7, 2004
Journal of Experimental Biology 207, 3865-3871 (2004)
Published by The Company of Biologists 2004
doi: 10.1242/jeb.01225

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Acclimatization to 4100 m does not change capillary density or mRNA expression of potential angiogenesis regulatory factors in human skeletal muscle

Carsten Lundby^1,*, Henriette Pilegaard², Jesper L. Andersen³, Gerrit van Hall¹, Mikael Sander¹ and Jose A. L. Calbet^1,4

¹ The Copenhagen Muscle Research Centre at Rigshospitalet section 7652, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
² The August Krogh Institute, University of Copenhagen, Denmark
³ Rigshospitalet Section 9312, University of Las Palmas de Gran Canaria, Spain
⁴ Department of Physical Education, University of Las Palmas de Gran Canaria, Spain

^* Author for correspondence (e-mail: carsten{at}cmrc.dk)

Accepted 3 August 2004

Increased skeletal muscle capillary density would be a logical adaptive mechanism to chronic hypoxic exposure. However, animal studies have yielded conflicting results, and human studies are sparse. Neoformation of capillaries is dependent on endothelial growth factors such as vascular endothelial growth factor (VEGF), a known target gene for hypoxia inducible factor 1 (HIF-1). We hypothesised that prolonged exposure to high altitude increases muscle capillary density and that this can be explained by an enhanced HIF-1 expression inducing an increase in VEGF expression. We measured mRNA levels and capillary density in muscle biopsies from vastus lateralis obtained in sea level residents (SLR; N=8) before and after 2 and 8 weeks of exposure to 4100 m altitude and in Bolivian Aymara high-altitude natives exposed to approximately 4100 m altitude (HAN; N=7). The expression of HIF-1 or VEGF mRNA was not changed with prolonged hypoxic exposure in SLR, and both genes were similarly expressed in SLR and HAN. In SLR, whole body mass, mean muscle fibre area and capillary to muscle fibre ratio remained unchanged during acclimatization. The capillary to fibre ratio was lower in HAN than in SLR (2.4±0.1 vs 3.6±0.2; P<0.05). In conclusion, human muscle VEGF mRNA expression and capillary density are not significantly increased by 8 weeks of exposure to high altitude and are not increased in Aymara high-altitude natives compared with sea level residents.

Key words: transcription, skeletal muscle, capillary density, hypoxia, HIF-1, VEGF

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