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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doaj-5484fa6659054e86b9d6fc151b7a7d542020-11-24T20:40:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013884710.1371/journal.pone.0138847Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia.Alban LongchampFlorent AllagnatFlorian AlonsoChristopher KupplerCéline DubuisCharles-Keith OzakiJames R MitchellScott BerceliJean-Marc CorpatauxSébastien DégliseJacques-Antoine HaefligerVenous 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.http://europepmc.org/articles/PMC4580578?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alban Longchamp Florent Allagnat Florian Alonso Christopher Kuppler Céline Dubuis Charles-Keith Ozaki James R Mitchell Scott Berceli Jean-Marc Corpataux Sébastien Déglise Jacques-Antoine Haefliger |
spellingShingle |
Alban Longchamp Florent Allagnat Florian Alonso Christopher Kuppler Céline Dubuis Charles-Keith Ozaki James R Mitchell Scott Berceli Jean-Marc Corpataux Sébastien Déglise Jacques-Antoine Haefliger Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia. PLoS ONE |
author_facet |
Alban Longchamp Florent Allagnat Florian Alonso Christopher Kuppler Céline Dubuis Charles-Keith Ozaki James R Mitchell Scott Berceli Jean-Marc Corpataux Sébastien Déglise Jacques-Antoine Haefliger |
author_sort |
Alban Longchamp |
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. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
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. |
url |
http://europepmc.org/articles/PMC4580578?pdf=render |
work_keys_str_mv |
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