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1 Medicine, Division of Clinical Physiology Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
2 Deptartment of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Cell and Molecular Biology , Karolinska Institutet, Stockholm, Sweden
3 Department of Medicine, Atherosclerosis Research Unit, King Gustav V Research Institute, Karolinska Institutet, Stockholm, Sweden
4 Department of Laboratory Medicine, Division of Clinical Physiology Karolinska University Hospital, Stockholm, Sweden; Department of Physiology and Pharamacology, Stockholm, Sweden
5 Deptartment of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden
6 Department of Laboratory Medicine, Division of Clinical Physiology Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
* To whom correspondence should be addressed. E-mail: thomas.gustafsson{at}ki.se.
The aims of this study were (1) to characterize changes in matrix metalloproteinase (MMP), endostatin and VEGF-A expression in skeletal muscle in response to a single bout of exercise in humans; and (2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest, and immediately and 120 min after exercise. In the muscle biopsies measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and TIMP; VEGF and endostatin protein levels; MMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle and the plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels were induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus, (1) a single bout of exercise activated the MMP-system without any resulting change in tissue endostatin protein levels following exercise; (2) and the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Othermechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.
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