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J Appl Physiol 102: 2346-2351, 2007. First published January 25, 2007; doi:10.1152/japplphysiol.00822.2006
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A single bout of exercise activates matrix metalloproteinase in human skeletal muscle

E. Rullman,1,2 H. Rundqvist,2,3 D. Wågsäter,4 H. Fischer,1,2 P. Eriksson,4 C. J. Sundberg,2 E. Jansson,1 and T. Gustafsson1,2

1Department of Laboratory Medicine, Division of Clinical Physiology, and 2Department of Physiology and Pharmacology, 3Department of Cell and Molecular Biology, and 4Department of Medicine, Atherosclerosis Research Unit, King Gustav V Research Institute, Karolinska University Hospital; Karolinska Institutet, Stockholm, Sweden

Submitted 26 July 2006 ; accepted in final form 25 January 2007

The aims of this study were 1) to characterize changes in matrix metalloproteinase (MMP), endostatin, and vascular endothelial growth factor (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 tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and 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 or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was 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, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.

vascular endothelial growth factor-A; endostatin; gene expression; matrix metalloproteinase-9



Address for reprint requests and other correspondence: T. Gustafsson, Div. of Clinical Physiology C1-88, Karolinska Univ. Hospital, Huddinge, 141 86 Stockholm, Sweden (e-mail: thomas.gustafsson{at}ki.se)




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