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Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microar...

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Autores principales: Longchamp, Alban, Allagnat, Florent, Alonso, Florian, Kuppler, Christopher, Dubuis, Céline, Ozaki, Charles-Keith, Mitchell, James R., Berceli, Scott, Corpataux, Jean-Marc, Déglise, Sébastien, Haefliger, Jacques-Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580578/
https://www.ncbi.nlm.nih.gov/pubmed/26398895
http://dx.doi.org/10.1371/journal.pone.0138847
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author Longchamp, Alban
Allagnat, Florent
Alonso, Florian
Kuppler, Christopher
Dubuis, Céline
Ozaki, Charles-Keith
Mitchell, James R.
Berceli, Scott
Corpataux, Jean-Marc
Déglise, Sébastien
Haefliger, Jacques-Antoine
author_facet Longchamp, Alban
Allagnat, Florent
Alonso, Florian
Kuppler, Christopher
Dubuis, Céline
Ozaki, Charles-Keith
Mitchell, James R.
Berceli, Scott
Corpataux, Jean-Marc
Déglise, Sébastien
Haefliger, Jacques-Antoine
author_sort Longchamp, Alban
collection PubMed
description Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide (43)gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment.
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spelling pubmed-45805782015-10-01 Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia Longchamp, Alban Allagnat, Florent Alonso, Florian Kuppler, Christopher Dubuis, Céline Ozaki, Charles-Keith Mitchell, James R. Berceli, Scott Corpataux, Jean-Marc Déglise, Sébastien Haefliger, Jacques-Antoine PLoS One Research Article Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide (43)gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment. Public Library of Science 2015-09-23 /pmc/articles/PMC4580578/ /pubmed/26398895 http://dx.doi.org/10.1371/journal.pone.0138847 Text en © 2015 Longchamp et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Longchamp, Alban
Allagnat, Florent
Alonso, Florian
Kuppler, Christopher
Dubuis, Céline
Ozaki, Charles-Keith
Mitchell, James R.
Berceli, Scott
Corpataux, Jean-Marc
Déglise, Sébastien
Haefliger, Jacques-Antoine
Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia
title Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia
title_full Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia
title_fullStr Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia
title_full_unstemmed Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia
title_short Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia
title_sort connexin43 inhibition prevents human vein grafts intimal hyperplasia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580578/
https://www.ncbi.nlm.nih.gov/pubmed/26398895
http://dx.doi.org/10.1371/journal.pone.0138847
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