Received January 6, 2005
Revised January 28, 2005
Accepted after revision January 28, 2005

¹ National Institute of Fitness and Sports

^* To whom correspondence should be addressed. E-mail: waga{at}nifs-k.ac.jp.

	Abstract

Capillary supply of skeletal muscle decreases during denervation. To gain insight into the regulation of this process, we investigated capillary supply and gene expression of angiogenesis-related factors in mouse gastrocnemius muscle following denervation for four months. Frozen transverse sections were stained for alkaline phosphatase to detect endogenous enzyme in the capillary endothelium. The mRNA for angiogenesis-related factors including hypoxia inducible factor-1(HIF-1), vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/Flk-1), fms-like tyrosine kinase (Flt-1), angiopoietin-1, and tyrosine kinase with Ig and EGF homology domain 2 (Tie-2) was analyzed using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The fiber cross-sectional area after denervation was about 20% of the control value, and the capillary-to-fiber ratio was significantly lower in denervated than in control muscles. The number of capillaries around each fiber also decreased to about 40% of the control value. These observations suggest that muscle capillarity decreases in response to chronic denervation. RT-PCR analysis showed that the expression of VEGF mRNA was lower in denervated than in control muscles, while the expression of HIF-1 mRNA remained unchanged. The expression levels of the KDR/Flk-1 and Flt-1 genes were decreased in the denervated muscle. The expression levels of angiopoietin-1 but not Tie-2 genes were decreased in the denervated muscle. These findings indicate that reduction in the expression of mRNAs in the VEGF/KDR/Flk-1 and Flt-1 as well as angiopoietin-1/Tie-2 signal pathways might be one of the reasons for the capillary regression during chronic denervation.

Key Words: Capillary, Denervation, Muscle