Urban Deutsch

Publications (2)11.26 Total impact

• Source

  Available from: Fanny Robbesyn

  Article: Estrogen-stimulated endothelial repair requires osteopontin.

  Laetitia Lam Shang Leen, Cédric Filipe, Audrey Billon, Barbara Garmy-Susini, Sandra Jalvy, Fanny Robbesyn, Danièle Daret, Cécile Allières, Susan R Rittling, Nikos Werner, Georg Nickenig, Urban Deutsch, Cécile Duplàa, Pascale Dufourcq, Françoise Lenfant, Claude Desgranges, Jean-François Arnal, Alain-Pierre Gadeau
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  ABSTRACT: 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. 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. 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.
  Arteriosclerosis Thrombosis and Vascular Biology 10/2008; 28(12):2131-6. · 6.37 Impact Factor
• Article: Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4- and frizzled 7-dependent pathway: role in neovessel formation.

  Pascale Dufourcq, Lionel Leroux, Jérome Ezan, Betty Descamps, Jean-Marie Daniel Lamazière, Pierre Costet, Caroline Basoni, Catherine Moreau, Urban Deutsch, Thierry Couffinhal, Cécile Duplàa
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  ABSTRACT: Consistent with findings of Wnt pathway members involved in vascular cells, a role for Wnt/Frizzled signaling has recently emerged in vascular cell development. Among the few Wnt family members implicated in vessel formation in adult, Wnt7b and Frizzled 4 have been shown as involved in vessel formation in the lung and in the retina, respectively. Our previous work has shown a role for secreted Frizzled-related protein-1 (sFRP-1), a proposed Wnt signaling inhibitor, in neovascularization after an ischemic event and demonstrated its role as a potent angiogenic factor. However the mechanisms involved have not been investigated. Here, we show that sFRP-1 treatment increases endothelial cell spreading on extracellular matrix as revealed by actin stress fiber reorganization in an integrin-dependent manner. We demonstrate that sFRP-1 can interact with Wnt receptors Frizzled 4 and 7 on endothelial cells to transduce downstream to cellular machineries requiring Rac-1 activity in cooperation with GSK-3beta. sFRP-1 overexpression in endothelium specifically reversed the inactivation of GSK-3 beta and increased neovascularization in ischemia-induced angiogenesis in mouse hindlimb. This study illustrates a regulated pathway by sFRP-1 involving GSK-3beta and Rac-1 in endothelial cell cytoskeletal reorganization and in neovessel formation.
  American Journal Of Pathology 02/2008; 172(1):37-49. · 4.89 Impact Factor