title: [The pro-angiogenesis effect of Pitavastatin in the Klotho gene-knockout mice].
abstract: OBJECTIVE
  To discuss the effect of Pitavastatin on angiogenesis in vivo and its mechanism in Klotho heterozygous deficient mice.
  
  
  METHODS
  The heterozygous deficient Klotho mice (kl +/-) and wild mice (kl +/+) from the same litter were used to establish the animal model of hind-limb ischemia and grouped into control and Pitavastatin group, respectively. Hind-limb blood flow was evaluated using Laser Doppler perfusion imager (LDPI) before treatment and after operation of hind-limbs. The capillaries in muscle of limbs were counted by means of CD-31 labeled immuno-fluorescence. The phosphorylation of Akt (Protein kinase B) in cells was measured by direct immunohistochemical technique. The expression of vascular endothelial growth factors (VEGFs) in muscle of limbs was assessed using Western blotting.
  
  
  RESULTS
  After treatment of Pitavastatin, the blood flow in ischemic limbs of the Kl +/- and wild mice improved obviously, the ratio of blood flow area in ischemic limb to that in non-ischemic limb increased and the density of capillaries increased in ischemic limbs of the Kl +/- and wild mice. Pitavastatin enhanced the phosphorylation of Akt and the expression of VEGF in ischemic limbs of the Kl +/- and wild mice.
  
  
  CONCLUSIONS
  Pitavastatin has the pro-angiogenesis effect in vivo and the VEGF-p-Akt-NO pathway may be involved in the mechanism of the effect of Pitavastatin.
authors.affiliation: Department of Circulatory Medicine, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Yue-Lan
authors.initials: YL
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Tian
authors.forename: Zi-Xin
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Ding-Yin
authors.initials: DY
authors.lastname: Zeng
authors.forename: Guo-Xian
authors.initials: GX
authors.lastname: Qi
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D006579:Heterozygote; D007511:Ischemia; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011804:Quinolines / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D011804:Quinolines; D042461:Vascular Endothelial Growth Factor A; C108475:pitavastatin