title: Estrogen-stimulated endothelial repair requires osteopontin.
abstract: OBJECTIVE
  Estradiol (E(2)) is known to accelerate reendothelialization and thus prevent intimal thickening and in-stent restenosis after angioplasty. Transplantation experiments with ERalpha(-/-) mice have previously shown that E(2) acts through local and bone marrow cell compartments to enhance endothelial healing. However, the downstream mechanisms induced by E(2) to mediate endothelial repair are still poorly understood.
  
  
  RESULTS
  We show here that after endovascular carotid artery injury, E(2)-enhanced endothelial repair is lost in osteopontin-deficient mice (OPN(-/-)). Transplantation of OPN(-/-) bone marrow into wild-type lethally irradiated mice, and vice versa, suggested that osteopontin plays a crucial role in both the local and the bone marrow actions of E(2). In the vascular compartment, using transgenic mice expressing doxycyclin regulatable-osteopontin, we show that endothelial cell specific osteopontin overexpression mimics E(2)-enhanced endothelial cell migration and proliferation in the regenerating endothelium. In the bone marrow cell compartment, we demonstrate that E(2) enhances bone marrow-derived mononuclear cell adhesion to regenerating endothelium in vivo, and that this effect is dependent on osteopontin.
  
  
  CONCLUSIONS
  We demonstrate here that E(2) acceleration of the endothelial repair requires osteopontin, both for bone marrow-derived cell recruitment and for endothelial cell migration and proliferation.
authors.affiliation: INSERM U828, University of Bordeaux Victor Ségalen, IFR4, Bordeaux, France.
authors.forename: Laetitia Lam Shang
authors.initials: LL
authors.lastname: Leen
authors.forename: Cédric
authors.initials: C
authors.lastname: Filipe
authors.forename: Audrey
authors.initials: A
authors.lastname: Billon
authors.forename: Barbara
authors.initials: B
authors.lastname: Garmy-Susini
authors.forename: Sandra
authors.initials: S
authors.lastname: Jalvy
authors.forename: Fanny
authors.initials: F
authors.lastname: Robbesyn
authors.forename: Danièle
authors.initials: D
authors.lastname: Daret
authors.forename: Cécile
authors.initials: C
authors.lastname: Allières
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rittling
authors.forename: Nikos
authors.initials: N
authors.lastname: Werner
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
authors.forename: Cécile
authors.initials: C
authors.lastname: Duplàa
authors.forename: Pascale
authors.initials: P
authors.lastname: Dufourcq
authors.forename: Françoise
authors.initials: F
authors.lastname: Lenfant
authors.forename: Claude
authors.initials: C
authors.lastname: Desgranges
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.forename: Alain-Pierre
authors.initials: AP
authors.lastname: Gadeau
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053495:Osteopontin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology
chemical_list: C506896:Spp1 protein, mouse; D053495:Osteopontin; D004958:Estradiol