Increased expression of vascular endothelial growth factor in human skeletal muscle in response to short-term one-legged exercise training

Abstract

The effects of short-term exercise training on vascular endothelial growth factor (VEGF) and one of its regulatory transcription factors, the hypoxia inducible factor 1 (HIF-1) subunit, were studied in eight healthy males. Muscle and blood samples were obtained before the 1st, and 24 h after the 7th training session. VEGF and HIF-1 mRNA were analysed using RT-PCR, VEGF mRNA localization with in situ hybridization and VEGF protein with ELISA. Concurrent increases in VEGF mRNA and protein levels were observed in skeletal muscle, and the mRNA was expressed within the skeletal muscle fibres and in cells in the interstitium. These data support the idea of a pretranslational regulation of exercise-induced changes in VEGF mRNA, and indicate that increased VEGF protein expression is an early event in skeletal muscle adaptation to training. Furthermore, different cell types may act as sources for the production of angiogenic factors in response to exercise. The levels of HIF-1 mRNA subunits did not change, suggesting no change in HIF-1 mRNA transcript levels in the regulation of training-induced VEGF expression. In contrast to increased tissue VEGF expression, the arterial and femoral venous plasma levels of VEGF were decreased by training, which may indicate an exercise-induced enhancement of the peripheral uptake of VEGF.

Effect of intermittent hypoxic training on HIF gene expression in human skeletal muscle and leukocytes

“…2). This observation has already been reported in previous studies (Gustafsson et al 1999;Gustafsson et al 2002;Ameln et al 2005). The lack of vEGF mRNA changes in IHE muscle has been already found by Friedmann et al (2003) during hypoxic, normobaric training.…”

“…Studies have shown the crucial role played by HIF-1 in vEGF activation during hypoxia (Forsythe et al 1996;Däpp et al 2006). Moreover, relationships between the amounts of HIF-1 protein and vEGF protein as well as levels of HIF-1 mRNA and vEGF mRNA in human skeletal muscle were found at rest and during exercise (Gustafsson et al 1999(Gustafsson et al , 2002Ookawara et al 2002). We did not Wnd similar results in human skeletal muscle concerning a potential link between vEGF and HIF-1 variations of expression for both types of training conditions.…”

“…Indeed, a longer training program (i.e., 6 weeks) signiWcantly up regulated hif-1 gene expression in vastus lateralis by 104% , whereas it induced a down regulation of hif-1 gene expression in leukocytes (Mounier et al unpublished data). Moreover, a 6-week period of hypoxic training (30 min cycling at 3,850 m/day, 5 days/week) induced a signiWcant accumulation of HIF-1 transcripts in vastus lateralis (Vogt et al 2001) whereas a normoxic one leg training program (45 min/day, 7 times in 10 days) had no eVect on HIF-1 mRNA in this muscle (Gustafsson et al 2002).…”

Exercise Training and Peripheral Arterial Disease

“…Chronic electrical stimulation of rat skeletal muscle induced an early increase in VEGF mRNA which declined over the 21 d of study (340). An immediate increase in VEGF mRNA was also seen in rat skeletal muscle in response to a single exercise bout (91, 294) and in rat (296) and human (328) skeletal muscle in response to short-term exercise training. TGF-β1 mRNA has also been reported to be upregulated by a single bout of exercise or by short-term training, although the upregulation is not as striking as that of VEGF mRNA (91, 294, 296).…”

“…The elevation in VEGF mRNA and protein observed with an acute exercise bout persists after repeated exercise sessions (26, 328, 332, 340, 762). However, in humans, the response of VEGFA mRNA to a single bout of exercise appears to be blunted by long term training (398, 756).…”