In vivo modulation of Nogo-B attenuates neointima formation.
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.
Kritz
Angelika B
AB
British Heart Foundation Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, UK. ab11f@clinmed.gla.ac.uk
Yu
Jun
J
Wright
Paulette L
PL
Wan
Song
S
George
Sarah J
SJ
Halliday
Crawford
C
Kang
Ning
N
Sessa
William C
WC
Baker
Andrew H
AH
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
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse
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