Exercise up regulates VEGF transcription in mouse gastrocnemius muscle

Abstract

Vascular endothelial growth factor (VEGF) is important for maintaining capillary number in mouse skeletal muscle. VEGF expression is controlled in part by HIF-1, which may be up regulated by both hypoxia and/or exercise. In this study, we used mice that have been engineered with a VEGF promoter-luciferase construct to examine how hypoxia, exercise or both affect VEGF transcription. Mice (adults, 5 months old) were separated into four groups (n = 4): hypoxia (10%)-rest (HR); hypoxia-exercise (HE); normoxia-rest (NR); and normoxia-exercise (NE). Exercising mice ran on a treadmill (10 degrees) for an hour at 18 m/min while exposed to hypoxia or at 30 m/min in normoxia. After the exercise bout or hypoxic exposure, mice rested an additional hour in normoxia or hypoxia before the gastrocnemius muscle was harvested for analysis. Using real time RT-PCR, we found that exercise significantly increased VEGF mRNA levels greater than 3 fold in both hypoxia and normoxia: HE=6.0±1.1 vs. HR= 1.8±0.3 and NE=5.9±0.6 vs. NR=1.6±0.1 (p<0.001). VEGF transcription measured by luciferase activity was also increased (~ 50%) by exercise in hypoxia and normoxia: HE=54.2±3.0 vs. HR=36.7±3.4 and NE=52.5±3.8 vs. NR=33.8±4.9 (p<0.01). There were no differences in VEGF transcription between the HR and NR groups using either assay. These data suggest that exercise up regulates VEGF transcriptional activity in mouse gastrocnemius muscle. Furthermore, 10% hypoxic exposure alone or in combination with an exercise stimulus did not enhance VEGF expression through either a transcriptional or post-transcriptional mechanism. This research was supported by NIH HL17731, HL84281-01, and HL07212-30.