Estrogen-stimulated endothelial repair requires osteopontin.
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.
Leen
Laetitia Lam Shang
LL
INSERM U828, University of Bordeaux Victor Ségalen, IFR4, Bordeaux, France.
Filipe
Cédric
C
Billon
Audrey
A
Garmy-Susini
Barbara
B
Jalvy
Sandra
S
Robbesyn
Fanny
F
Daret
Danièle
D
Allières
Cécile
C
Rittling
Susan R
SR
Werner
Nikos
N
Nickenig
Georg
G
Deutsch
Urban
U
Duplàa
Cécile
C
Dufourcq
Pascale
P
Lenfant
Françoise
F
Desgranges
Claude
C
Arnal
Jean-François
JF
Gadeau
Alain-Pierre
AP
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
C506896:Spp1 protein, mouse; D053495:Osteopontin; D004958:Estradiol