title: [Inhibitory effect of von Willebrand factor-cleaving protease on angiogenesis].
abstract: OBJECTIVE
  To investigate the inhibitory effect of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with thrombospondin-1 repeats (ADAMTS13)on angiogenesis induced by vascular endothelial growth factor (VEGF)in vitro and in vivo.
  
  
  METHODS
  Cell proliferation assay, differentiation (tube formation)assay and wound migration assay were performed by using human umbilical vein endothelial cells (HUVECs)to explore the effect of ADAMTS13 on angiogenesis in vitro. Cells were treated with different concentrations of ADAMTS13 (1, 5, 25, 50 and 100 nmol/L)and the number of cells was counted via MTT assay. In addition, effect of ADAMTS13 on differentiation was assessed by measuring the length of capillary-like tube structures formed by HUVECS in matrigel. Effect of ADAMTS13 on HUVEC migration was assessed via calculation of wound healing distance after 8 hrs culture with VEGF or ADAMTS13. Chick embryo chorioallantoic membrane (CAM) assay and Matrigel plug assay were performed to investigate the effect of ADAMTS13 on angiogenesis in vivo.
  
  
  RESULTS
  ADAMTS13 significantly inhibited the proliferation of HUVECs induced by VEGF in a dose-dependent manner. Migration distance of HUVECs was (79 ± 22) μm in control group, (250 ± 8)μm in VEGF-treated group and (170 ± 23)μm in VEGF and ADAMTS13 cotreated-group after 8 hrs, respectively. The tube length is (450.6 ± 16.6)% in VEGF-treated group and (235.3 ± 19.0)% in VEGF and ADAMTS13 cotreated-group of that of control group after HUVECs cultured in matrigel for 16 hrs. The number of blood vessels decreased after treatment with ADAMTS13 in CAM assay. The number of blood vessels was (228.2 ± 10.8)%, (69.2 ± 21.1)%, (184.6 ± 15.2)% in VEGF treated-group, ADAMTS13 treated-group and VEGF and ADAMTS13 cotreated-group of that of control group, respectively. Formation of capillary-like network in matrigel plugs containing VEGF was reduced to 43.5% by ADAMTS13 in matrigel plug assay in mouse model.
  
  
  CONCLUSIONS
  ADAMTS13 inhibits the HUVECs proliferation, differentiation and migration in vitro. ADAMTS13 inhibits chick embryos vascularization and formation of capillary-like network in vivo.
authors: Medical Research Center, Yanbian University Hospital, Yanji 133000, China.
authors: Chunhai
authors: C
authors: Jin
authors: Medical Research Center, Yanbian University Hospital, Yanji 133000, China.
authors: Shuang
authors: S
authors: Wang
authors: Medical Research Center, Yanbian University Hospital, Yanji 133000, China.
authors: Yanhong
authors: Y
authors: Zhao
authors: Medical Research Center, Yanbian University Hospital, Yanji 133000, China.
authors: Shengyu
authors: S
authors: Jin
authors: Medical Research Center, Yanbian University Hospital, Yanji 133000, China.
authors: Hua
authors: H
authors: Li
mesh_terms: D051722:ADAM Proteins / Q000494:pharmacology*; D000071120:ADAMTS13 Protein; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane; D003094:Collagen; D004338:Drug Combinations; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D007797:Laminin; D051379:Mice; D018919:Neovascularization, Physiologic; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human