title: Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia.
abstract: 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.
authors.affiliation: Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Laboratory of Experimental Medicine, Lausanne, Switzerland; Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Alban
authors.initials: A
authors.lastname: Longchamp
authors.affiliation: Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Laboratory of Experimental Medicine, Lausanne, Switzerland.
authors.forename: Florent
authors.initials: F
authors.lastname: Allagnat
authors.affiliation: Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Laboratory of Experimental Medicine, Lausanne, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Alonso
authors.affiliation: Malcom Randall Veterans Affairs Medical Center and the Division of Vascular and Endovascular Surgery, University of Florida College of Medicine, Gainesville, Florida, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kuppler
authors.affiliation: Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Laboratory of Experimental Medicine, Lausanne, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Dubuis
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Charles-Keith
authors.initials: CK
authors.lastname: Ozaki
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: James R
authors.initials: JR
authors.lastname: Mitchell
authors.affiliation: Malcom Randall Veterans Affairs Medical Center and the Division of Vascular and Endovascular Surgery, University of Florida College of Medicine, Gainesville, Florida, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Berceli
authors.affiliation: Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Laboratory of Experimental Medicine, Lausanne, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Corpataux
authors.affiliation: Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Laboratory of Experimental Medicine, Lausanne, Switzerland.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Déglise
authors.affiliation: Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Laboratory of Experimental Medicine, Lausanne, Switzerland.
authors.forename: Jacques-Antoine
authors.initials: JA
authors.lastname: Haefliger
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018031:Connexin 43 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology*; D058017:Vascular Grafting; D014680:Veins / Q000637:transplantation*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human