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Eph-B4 prevents venous adaptive remodeling in the adult arterial environment

Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and i...

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Autores principales: Muto, Akihito, Yi, Tai, Harrison, Kenneth D., Dávalos, Alberto, Fancher, Tiffany T., Ziegler, Kenneth R., Feigel, Amanda, Kondo, Yuka, Nishibe, Toshiya, Sessa, William C., Dardik, Alan
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058579/
https://www.ncbi.nlm.nih.gov/pubmed/21339325
http://dx.doi.org/10.1084/jem.20101854
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author Muto, Akihito
Yi, Tai
Harrison, Kenneth D.
Dávalos, Alberto
Fancher, Tiffany T.
Ziegler, Kenneth R.
Feigel, Amanda
Kondo, Yuka
Nishibe, Toshiya
Sessa, William C.
Dardik, Alan
author_facet Muto, Akihito
Yi, Tai
Harrison, Kenneth D.
Dávalos, Alberto
Fancher, Tiffany T.
Ziegler, Kenneth R.
Feigel, Amanda
Kondo, Yuka
Nishibe, Toshiya
Sessa, William C.
Dardik, Alan
author_sort Muto, Akihito
collection PubMed
description Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment. We show that stimulation of Eph-B4 signaling, either via ligand stimulation or expression of a constitutively active Eph-B4, inhibits venous wall thickening and preserves venous identity; conversely, reduction of Eph-B4 signaling is associated with increased venous wall thickness. Stimulated Eph-B4 associates with caveolin-1 (Cav-1); loss of Cav-1 or Eph-B4 kinase function abolishes inhibition of vein graft thickening. These results show that Eph-B4 is active in adult veins and regulates venous remodeling. Eph-B4–Cav-1–mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults.
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spelling pubmed-30585792011-09-14 Eph-B4 prevents venous adaptive remodeling in the adult arterial environment Muto, Akihito Yi, Tai Harrison, Kenneth D. Dávalos, Alberto Fancher, Tiffany T. Ziegler, Kenneth R. Feigel, Amanda Kondo, Yuka Nishibe, Toshiya Sessa, William C. Dardik, Alan J Exp Med Article Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment. We show that stimulation of Eph-B4 signaling, either via ligand stimulation or expression of a constitutively active Eph-B4, inhibits venous wall thickening and preserves venous identity; conversely, reduction of Eph-B4 signaling is associated with increased venous wall thickness. Stimulated Eph-B4 associates with caveolin-1 (Cav-1); loss of Cav-1 or Eph-B4 kinase function abolishes inhibition of vein graft thickening. These results show that Eph-B4 is active in adult veins and regulates venous remodeling. Eph-B4–Cav-1–mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults. The Rockefeller University Press 2011-03-14 /pmc/articles/PMC3058579/ /pubmed/21339325 http://dx.doi.org/10.1084/jem.20101854 Text en © 2011 Muto et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Muto, Akihito
Yi, Tai
Harrison, Kenneth D.
Dávalos, Alberto
Fancher, Tiffany T.
Ziegler, Kenneth R.
Feigel, Amanda
Kondo, Yuka
Nishibe, Toshiya
Sessa, William C.
Dardik, Alan
Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
title Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
title_full Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
title_fullStr Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
title_full_unstemmed Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
title_short Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
title_sort eph-b4 prevents venous adaptive remodeling in the adult arterial environment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058579/
https://www.ncbi.nlm.nih.gov/pubmed/21339325
http://dx.doi.org/10.1084/jem.20101854
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