In vivo modulation of Nogo-B attenuates neointima formation

Mol Ther. 2008 Nov;16(11):1798-804. doi: 10.1038/mt.2008.188. Epub 2008 Sep 9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology
  • Carotid Arteries / surgery
  • Cell Proliferation
  • Cells, Cultured
  • Chemotaxis
  • Constriction, Pathologic / pathology
  • Constriction, Pathologic / prevention & control
  • Disease Models, Animal
  • Femoral Artery / metabolism
  • Femoral Artery / pathology
  • Gene Transfer Techniques
  • Genetic Vectors
  • Graft Occlusion, Vascular / pathology
  • Graft Occlusion, Vascular / prevention & control
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Myelin Proteins / biosynthesis*
  • Myelin Proteins / genetics
  • Nogo Proteins
  • Saphenous Vein / metabolism
  • Saphenous Vein / pathology
  • Swine
  • Tunica Intima / metabolism*
  • Tunica Intima / pathology
  • Tunica Media / metabolism*
  • Tunica Media / pathology


  • Myelin Proteins
  • Nogo Proteins
  • RTN4 protein, human
  • Rtn4 protein, mouse