title: Capillary supply and gene expression of angiogenesis-related factors in murine skeletal muscle following denervation.
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 4 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-1alpha (HIF-1alpha), 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 epidermal growth factor(EGF) homology domain 2 (Tie-2), was analysed using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The fibre cross-sectional area after denervation was about 20% of the control value, and the capillary to fibre ratio was significantly lower in denervated than in control muscles. The number of capillaries around each fibre 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-1alpha 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.
authors.affiliation: Department of Physiological Sciences, National Institute of Fitness and Sports, Shiromizu-cho 1, Kanoya, Kagoshima 891-2393, Japan. waga@nifs-k.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Wagatsuma
authors.forename: H
authors.initials: H
authors.lastname: Tamaki
authors.forename: F
authors.initials: F
authors.lastname: Ogita
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D002196:Capillaries / Q000166:cytology*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009121:Muscle Denervation / Q000379:methods*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*
chemical_list: D042501:Angiogenic Proteins; D009124:Muscle Proteins