title: Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo.
abstract: OBJECTIVE
  Activation of fully differentiated vascular cells using angiogenic genes can lead to phenotypic changes resulting in formation of new blood vessels. We tested whether Ang-1 gene transfer to endothelial cells (EC) activates these cells.
  
  
  RESULTS
  EC and SMC were transduced using retroviral or adenoviral vectors to produce Ang-1 or vascular endothelial growth factor (VEGF). EC Tie-2 receptor was phosphorilated by autologous secretion of Ang-1. Transduced EC and SMC sprouting capacity was tested using collagen embedded spheroids assay and capacity to produce arteriogenesis was tested in a hind limb model of ischemia. EC expressing Ang-1 in the presence of SMC expressing VEGF exhibited high levels of sprouting of the two cell types. Flow and numbers of arteries were increased after transduced cells implantation in vivo.
  
  
  CONCLUSIONS
  Autologous secretion of Ang-1 by transduced EC resulted in Tie-2 activation and in the presence of SMC expressing VEGF resulted in coordinated sprouting in vitro and increase in flow and number of arteries in vivo.
authors.affiliation: MultiGene Vascular Systems Ltd, Lady Davis Carmel Medical Center, Haifa, Israel.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Gluzman
authors.forename: Belly
authors.initials: B
authors.lastname: Koren
authors.forename: Meir
authors.initials: M
authors.lastname: Preis
authors.forename: Tzafra
authors.initials: T
authors.lastname: Cohen
authors.forename: Adili
authors.initials: A
authors.lastname: Tsaba
authors.forename: Francois-Loic
authors.initials: FL
authors.lastname: Cosset
authors.forename: Rona
authors.initials: R
authors.lastname: Shofti
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Moshe Y
authors.initials: MY
authors.lastname: Flugelman
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D018076:DNA, Complementary / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D012190:Retroviridae / Q000235:genetics; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D018076:DNA, Complementary; D042461:Vascular Endothelial Growth Factor A