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126Muscle-specific expression of HIF in human skeletal muscle.
Mounier R; Klarlund Pedersen B; Plomgaard P
Exp Physiol 2010; 95(8): 899-907
PubMed ID: 20494919

Skeletal muscle is well known to exhibit a high degree of plasticity depending on environmental changes such as various oxygen concentrations. Studies of the oxygen-sensitive subunit a of the hypoxia inducible factor-1 (HIF-1) are difficult due to the large variety of functionally diverse muscle fibers that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analyzed HIF-1alpha mRNA and protein expression related to the fiber-type composition in untrained human skeletal muscle by obtaining muscle biopsies from triceps brachii (characterized by a high proportion of type II fibers), from soleus (characterized by a high proportion of type I fibers) and from vastus lateralis (characterized by an equal proportion of type I and II fibers). The hypothesis was that type I muscle fibres would have lower HIF-1 mRNA and protein due their higher oxidative capacity. We have shown, in normoxic conditions, a higher HIF-1alpha protein expression in predominantly oxidative muscles than in the predominantly glycolytic muscles. However, the HIF-1alpha mRNA expression pattern was not in agreement with the HIF-1alpha protein level. Interestingly, none of the HIF-1alpha target genes, like the most studied angiogenic factor involved in muscle angiogenesis VEGF, exhibited a muscle-fiber, specific-related mRNA expression at rest under normoxia. However, soleus presented a significant highest VEGF protein content than vastus lateralis and triceps muscle. In conclusion, we have shown that there are muscle-specific differences in HIF-1alpha and VEGF expression within human skeletal muscle at rest in normoxic conditions. Recent results, when combined with the findings described here, support a key role for HIF-1alpha in non-hypoxic conditions for maintaining muscle homeostasis.

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