Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia | Zendy

Alban Longchamp | Zendy; Florent Allagnat | Zendy; Florian Alonso | Zendy; Christopher Kuppler | Zendy; Céline Dubuis | Zendy; Charles-Keith Ozaki | Zendy; James R. Mitchell | Zendy; Scott A. Berceli | Zendy; Jean-Marc Corpataux | Zendy; Sébastien Déglise | Zendy; JacquesAntoine Haefliger | Zendy

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Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

Author(s) -

Alban Longchamp,

Florent Allagnat,

Florian Alonso,

Christopher Kuppler,

Céline Dubuis,

Charles-Keith Ozaki,

James R. Mitchell,

Scott A. Berceli,

Jean-Marc Corpataux,

Sébastien Déglise,

JacquesAntoine Haefliger

Publication year - 2015

Publication title -

plos one

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.99

H-Index - 332

ISSN - 1932-6203

DOI - 10.1371/journal.pone.0138847

Subject(s) - intimal hyperplasia , ex vivo , vascular smooth muscle , connexin , cell growth , microbiology and biotechnology , hyperplasia , gap junction , biology , in vivo , pathology , medicine , intracellular , endocrinology , smooth muscle , genetics

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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