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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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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. |
format | Online Article Text |
id | pubmed-4580578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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