|Institution:||University of Oslo|
|Full text PDF:||http://urn.nb.no/URN:NBN:no-26882
The effects of VEGF on skeletal muscle phenotype in adult rats. Skeletal muscle has an exceptional ability to adapt to different usage. Phenotype transformation is mainly dependent on the changes of firing pattern from motor neurones, but the exact signalling pathways are still not established. Vascular endothelial growth factor (VEGF) is an important secreted mitogen controlling several pathways that regulate processes such as embryonic vasculogenesis, angiogenesis, vascular permeability, cell migration and survival. Up-regulation of VEGF is seen in both tumour growth and hypertrophy in heart muscle, and it has been suggested that VEGF could contribute to the hypertrophy of the cardiomyocytes. The aim of this study is to investigate whether VEGF has a similar effect on skeletal muscle cells. I have over-expressed the isoform VEGF-A in the fast skeletal muscle extensor digtorum longus (EDL) in adult male Wistar rats. The over-expression was performed by somatic gene transfer, by electroporation. The effects on fibre type, capillarization, fibre cross sectional area and oxidative capacity were studied and analysed on serial of muscle sections. After fourteen days of VEGF over-expression, no change in fibre type distribution was observed as judged by immunohistochemistry. Histochemical analyses showed a significant increase in the number of capillaries around 2x and 2b by 9.5 % and 30.7 %, no change was observed in 2a fibres, but these already have a high number of capillaries. The cross sectional area of 2a and 2b fibres was significant increased by 12.4 % and 9.4 % respectively. Measurements of oxidative capacity by histochemical analyses indicate a significant increase in all fibre types, 2a, 2x and 2b, with a percent increase of 6.9 %, 13.0 % and 14.9 % respectively. All data are compared to normal and sham control fibres. Our data suggest that VEGF might not only influence capillarization, but also act back on the muscle fibres themselves as to induce hypertrophy and increased oxidative capacity.