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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Main Authors:	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
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580578/

id	pubmed-4580578
recordtype	oai_dc
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 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 43gap26 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
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
spellingShingle	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
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
title	Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia
title_short	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_sort	connexin43 inhibition prevents human vein grafts intimal hyperplasia
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 43gap26 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.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580578/
_version_	1613478901814657024

Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

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