Estrogen-stimulated endothelial repair requires osteopontin

Leen, Laetitia Lam Shang; Filipe, Cédric; Billon, Audrey; Garmy-Susini, Barbara; Jalvy, Sandra; Robbesyn, Fanny; Daret, Danièle; Allières, Cécile; Rittling, Susan R; Werner, Nikos; Nickenig, Georg; Deutsch, Urban; Duplàa, Cécile; Dufourcq, Pascale; Lenfant, Françoise; Desgranges, Claude; Arnal, Jean-François; Gadeau, Alain-Pierre (2008). Estrogen-stimulated endothelial repair requires osteopontin. Arteriosclerosis, thrombosis, and vascular biology, 28(12), pp. 2131-6. Philadelphia, Pa.: Lippincott Williams & Wilkins 10.1161/ATVBAHA.108.167965

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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. METHODS AND 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban






Lippincott Williams & Wilkins




Factscience Import

Date Deposited:

04 Oct 2013 15:05

Last Modified:

04 May 2014 23:20

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URI: (FactScience: 118530)

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