title: Angiopoietin-1 mediates adipose tissue-derived stem cell-induced inhibition of neointimal formation in rat femoral artery.
abstract: BACKGROUND
  Adipose tissue-derived stem cells (ASC) produce a variety of cytokines that potentially mediate the proangiogenic and antiapoptotic effects of the ASC. We examined whether ASC produced angiopoietin-1 (Ang1) and whether Ang1 functionally mediated ASC-induced suppression of neointimal formation.
  
  
  RESULTS
  Ang1 production was measured by enzyme-linked immunosorbent assay. Production of endogenous Ang1 by ASC was inhibited with small interfering RNA (siRNA) for Ang1. Overproduction of Ang1 was achieved with an adenovirus that expresses Ang1 (AdAng1). ASC expressing Ang1 siRNA, or AdAng1 were administered around the femoral artery after wire injury, and immunohistochemical analysis was performed to examine their effects on neointimal formation. ASC produced Ang1 in a time-dependent manner, especially when cultured in medium containing growth factors for vascular endothelial cells. When ASC were treated with Ang1 siRNA, the inhibitory effect of ASC on neointimal formation was significantly reduced. Knockdown of Ang1 significantly increased macrophage infiltration in the neointima, and significantly decreased endothelial regeneration. In contrast, forced expression of Ang1 using AdAng1 significantly suppressed neointimal formation and macrophage infiltration, and stimulated reendothelialization.
  
  
  CONCLUSIONS
  Ang1 was implicated in ASC-induced suppression of neointimal formation. The results also suggested that Ang1 inhibited neointimal formation via stimulation of reendothelialization and suppression of macrophage infiltration in the neointima.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Takahashi
authors.forename: Etsu
authors.initials: E
authors.lastname: Suzuki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kumano
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Oba
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sato
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005263:Femoral Artery / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D008297:Male; D058426:Neointima / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D042683:Angiopoietin-1; C467629:Angpt1 protein, rat