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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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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. |
format | Text |
id | pubmed-3058579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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