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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Published inPloS one Vol. 10; no. 9; p. e0138847
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 Journal Article
LanguageEnglish
Published United States Public Library of Science 23.09.2015
Public Library of Science (PLoS)
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Summary: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.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: AL F. Allagnat F. Alonso J-AH SD C-KO J-MC SB. Performed the experiments: AL F. Allagnat F. Alonso CK CD. Analyzed the data: AL F. Allagnat F. Alonso CK J-AH SD SB CD. Contributed reagents/materials/analysis tools: C-KO CK J-AH SD SB J-MC JM. Wrote the paper: AL F. Allagnat J-AH SD C-KO J-MC JM.
These authors contributed equally to this work as first authors.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0138847