title: Prostacyclin stimulated integrin-dependent angiogenic effects of endothelial progenitor cells and mediated potent circulation recovery in ischemic hind limb model.
abstract: BACKGROUND
  Prostacyclin (PGI2) enhances angiogenesis, especially in cooperation with bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the mechanisms of PGI2 in EPC-mediated angiogenesis in vivo remain unclear. The purpose of this study was to clarify the role of PGI2 in EPC-mediated angiogenesis using BM-specific IP deletion mice.
  
  
  RESULTS
  Hind limb ischemia (HLI) was induced in wild-type (WT) mice transplanted with IP-deleted BM (WT/BM(IP(-/-)). Recovery of blood flow (RBF) in WT/BM(IP(-/-)) was impaired for 28 days after HLI, whereas RBF in IP(-/-)/BM(WT) was attenuated for up to 7 days compared with WT/BM(WT). The impaired RBF in WT/BM(IP(-/-)) was completely recovered by intramuscular injection of WT EPCs but not IP(-/-) EPCs. The impaired effects of IP(-/-) EPCs were in accordance with reduced formation of capillary and arterioles in ischemic muscle. An ex vivo aortic ring assay revealed that microvessel formation was enhanced by accumulation/adhesion of EPCs to perivascular sites as pericytes. IP(-/-)EPCs, in which expression of integrins was decreased, had impaired production of angiogenic cytokines, adhesion to neovessels and their angiogenic effects. The small-interfering RNA (siRNA)-mediated knockdown of integrin β1 in WT EPCs attenuated adhesion to microvessels and their in vivo and in vitro angiogenic effects.
  
  
  CONCLUSIONS
  PGI2 may induce persistent angiogenic effects in HLI through adhesion of EPCs to perivascular sites of neovessels via integrins in addition to paracrine effects.
authors.affiliation: Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aburakawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kawabe
authors.forename: Motoi
authors.initials: M
authors.lastname: Okada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Akira
authors.initials: A
authors.lastname: Asanome
authors.forename: Maki
authors.initials: M
authors.lastname: Kabara
authors.forename: Motoki
authors.initials: M
authors.lastname: Matsuki
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takehara
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Okumura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Minami
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mizukami
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Yuhki
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ushikubi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hasebe
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D011464:Epoprostenol / Q000235:genetics / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D011982:Receptors, Prostaglandin; D011464:Epoprostenol