title: Prostaglandin I2 promotes recruitment of endothelial progenitor cells and limits vascular remodeling.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPCs) play an important role in the self-healing of a vascular injury by participating in the reendothelialization that limits vascular remodeling. We evaluated whether prostaglandin I(2) plays a role in the regulation of the function of EPCs to limit vascular remodeling.
  
  
  RESULTS
  EPCs (Lin(-)cKit(+)Flk-1(+) cells) were isolated from the bone marrow (BM) of wild-type (WT) mice or mice lacking the prostaglandin I(2) receptor IP (IP(-/-) mice). Reverse transcription-polymerase chain reaction analysis showed that EPCs among BM cells specifically express IP. The cellular properties of EPCs, adhesion, migration, and proliferation on fibronectin were significantly attenuated in IP-deficient EPCs compared with WT EPCs. In contrast, IP agonists facilitated these functions in WT EPCs, but not in IP-deficient EPCs. The specific deletion of IP in BM cells, which was performed by transplanting BM cells of IP(-/-) mice to WT mice, accelerated wire injury-mediated neointimal hyperplasia in the femoral artery. Notably, transfused WT EPCs, but not IP-deficient EPCs, were recruited to the injured vessels, participated in reendothelialization, and efficiently rescued the accelerated vascular remodeling.
  
  
  CONCLUSIONS
  These findings clearly indicate that the prostaglandin I(2)-IP system is essential for EPCs to accomplish their function and plays a critical role in the regulation of vascular remodeling.
authors.affiliation: Department of Pharmacology, Asahikawa Medical College, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kawabe
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Yuhki
authors.forename: Motoi
authors.initials: M
authors.lastname: Okada
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kanno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Tashiro
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Okumura
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Youko
authors.initials: Y
authors.lastname: Aburakawa
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takehara
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujino
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hasebe
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ushikubi
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D011464:Epoprostenol / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D044006:Receptors, Epoprostenol / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D005353:Fibronectins; D044006:Receptors, Epoprostenol; D011464:Epoprostenol