mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and hypoxia-inducible factor (HIF) subunits HIF-1 and HIF-1 in human skeletal muscle was studied during endurance exercise at different degrees of oxygen delivery. Muscle biopsies were taken before and after 45 min of one-legged knee-extension exercise performed under conditions of nonrestricted or restricted blood flow (~15-20% lower) at the same absolute workload. Exercise increased VEGF mRNA expression by 178% and HIF-1 by 340%, but not HIF-1 and FGF-2. No significant differences between the restricted and nonrestricted groups were observed. The exercise-induced increase in VEGF mRNA was correlated to the exercise changes in HIF-1 and HIF-1 mRNA. The changes in VEGF, HIF-1, and HIF-1 mRNAs were correlated to the exercise-induced increase in femoral venous plasma lactate concentration. It is concluded that 1) VEGF but not FGF-2 gene expression is upregulated in human skeletal muscle by a single bout of dynamic exercise and that there is a graded response in VEGF mRNA expression related to the metabolic stress and 2) the increase in VEGF mRNA expression correlates to the changes in both HIF-1 and HIF-1 mRNA.

ischemia; gene expression; vascular endothelial growth factor; fibroblast growth factor; hypoxia-inducible factor 1

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