A single bout of exercise activates matrix metalloproteinase in human skeletal muscle

Abstract

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.

Activation of the erythropoietin receptor in human skeletal muscle

“…A similar response has been demonstrated for VEGF-A (20), in which a higher interstitial level was observed during a single exercise bout (21). Such increase must be assumed to reflect an increase in bioavailability also described for other growth factors driven by exercise (22).…”

Endurance exercise activates matrix metalloproteinases in human skeletal muscle

“…Furthermore, expression and exercise-induced changes of MMP levels in human skeletal muscle have to our knowledge only one been explored in one earlier study. This study demonstrated that a single bout of exercise induced expression of MMP-9 mRNA as well as increased MMP-9 activity (29).…”

“…In addition to the welldocumented effects of MMPs on angiogenesis, several in vitro studies have shown that the bioavailability of various growth factors is increased by proteolytic cleavage of extracellular matrix molecules and binding proteins (8,9,21). Our laboratory, and others, have reported increases in the level of the rate-limiting angiogenic factor, vascular endothelial growth factor-A, in plasma and extracellular fluid after only a few minutes of exercise (16,17,29). This clearly demonstrates that growth factors may be stored and released without previous transcription under physiological conditions.…”

“…MMP-2, pro-MMP-9, and active MMP-9 distribution was determined from muscle biopsy homogenate before and 2 h after the first exercise bout, after 10 days of training, and after 5 wk of training. A detailed description of the protocol used has been published previously (29). Briefly, 25 g of protein homogenized in phosphate-buffer were diluted into 2ϫ Trisglycine SDS sample buffer and electrophoretically separated under nonreducing conditions.…”

The Long-Term Effects of Colostrum Supplementation and Sprint-Endurance Training on Plasma VEGF Levels in Male Wistar Rats

“…the involvement of various cells, signaling pathways, growth factors and receptors, 6 and eventually induces the growth of new blood vessels from pre-existing vessels via the 2 sprouting 7,8 and longitudinal splitting 1 modes. Vascular endothelial growth factor (VEGF) is the main mitogen involved in angiogenesis.…”