title: In vivo modulation of Nogo-B attenuates neointima formation.
abstract: Nogo-B was recently identified as a novel vascular marker; the normally high vascular expression of Nogo-B is rapidly lost following vascular injury. Here we assess the potential therapeutic effects of Ad-Nogo-B delivery to injured vessels in vivo. Nogo-B overexpression following Ad-Ng-B infection of vascular smooth muscle cells (VSMCs) was shown to block proliferation and migration in a dose-dependent manner in vitro. We next assessed the effects of Ad-Ng-B treatment on neointima formation in two in vivo models of acute vascular injury. Adventitial delivery of Ad-Ng-B to wire-injured murine femoral arteries led to a significant decrease in the intimal area [0.014 mm(2) versus 0.030 mm(2) (P = 0.049)] and the intima:media ratio [0.78 versus 1.67 (P = 0.038)] as compared to the effects of Ad-beta-Gal control virus at 21 days after injury. Similarly, lumenal delivery of Ad-Ng-B to porcine saphenous veins prior to carotid artery grafting significantly reduced the intimal area [2.87 mm(2) versus 7.44 mm(2) (P = 0.0007)] and the intima:media ratio [0.32 versus 0.55 (P = 0.0044)] as compared to the effects following the delivery of Ad- beta-Gal, at 28 days after grafting. Intimal VSMC proliferation was significantly reduced in both the murine and porcine disease models. Gene delivery of Nogo-B exerts a positive effect on vascular injury-induced remodeling and reduces neointimal development in two arterial and venous models of vascular injury.
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, UK. ab11f@clinmed.gla.ac.uk
authors.forename: Angelika B
authors.initials: AB
authors.lastname: Kritz
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Paulette L
authors.initials: PL
authors.lastname: Wright
authors.forename: Song
authors.initials: S
authors.lastname: Wan
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: George
authors.forename: Crawford
authors.initials: C
authors.lastname: Halliday
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D003251:Constriction, Pathologic / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000378:metabolism / Q000473:pathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics; D000070798:Nogo Proteins; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology; D013552:Swine; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism* / Q000473:pathology
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse
references.citation: Gene Ther. 2001 May;8(9):668-76
references.pmid: 11406761
references.citation: Ann Thorac Surg. 1998 May;65(5):1273-8
references.pmid: 9594850
references.citation: Neuron. 2003 Apr 24;38(2):187-99
references.pmid: 12718854
references.citation: J Am Coll Cardiol. 1993 Apr;21(5):1166-74
references.pmid: 8459072
references.citation: J Thorac Cardiovasc Surg. 1994 Sep;108(3):540-8
references.pmid: 8078347
references.citation: J Thorac Cardiovasc Surg. 2003 Dec;126(6):1972-7
references.pmid: 14688715
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10997-1002
references.pmid: 16835300
references.citation: J Mol Cell Cardiol. 2000 Nov;32(11):2097-104
references.pmid: 11040113
references.citation: Exp Cell Res. 2006 Jul 1;312(11):1983-8
references.pmid: 16687140
references.citation: J Mol Biol. 2003 Jan 10;325(2):299-323
references.pmid: 12488097
references.citation: Circulation. 2000 Jan 25;101(3):296-304
references.pmid: 10645926
references.citation: Int J Cancer. 2006 Oct 1;119(7):1648-53
references.pmid: 16646068
references.citation: J Comp Neurol. 2002 Nov 18;453(3):292-304
references.pmid: 12378589
references.citation: Nat Med. 2004 Apr;10(4):382-8
references.pmid: 15034570
references.citation: J Thorac Cardiovasc Surg. 1990 Mar;99(3):433-9
references.pmid: 2308361
references.citation: Vascul Pharmacol. 2007 Apr;46(4):293-301
references.pmid: 17207665
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1354-60
references.pmid: 17413036
references.citation: Mol Ther. 2004 May;9(5):689-98
references.pmid: 15120330
references.citation: J Thorac Cardiovasc Surg. 1997 Jul;114(1):38-45
references.pmid: 9240292
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jul;27(7):1500-10
references.pmid: 17510464
references.citation: Biochem Biophys Res Commun. 2007 Aug 17;360(1):128-34
references.pmid: 17585875
references.citation: Atherosclerosis. 1990 May;82(1-2):113-23
references.pmid: 2163252
references.citation: Lab Invest. 2002 Jul;82(7):825-32
references.pmid: 12118084
references.citation: Oncogene. 2001 Jul 5;20(30):3929-36
references.pmid: 11494121
references.citation: Methods Mol Med. 1999;30:271-83
references.pmid: 21341032
references.citation: Atherosclerosis. 2001 Apr;155(2):329-36
references.pmid: 11254903
references.citation: J Cell Physiol. 2003 Aug;196(2):312-8
references.pmid: 12811824
references.citation: Circulation. 2001 Nov 6;104(19):2289-94
references.pmid: 11696467
references.citation: Gene Ther. 2007 Mar;14(5):396-404
references.pmid: 17080182
references.citation: Oncogene. 2003 Mar 6;22(9):1390-9
references.pmid: 12618765
references.citation: Jpn J Surg. 1990 Nov;20(6):627-34
references.pmid: 2084287
references.citation: Circ Res. 1993 Nov;73(5):792-6
references.pmid: 8403250