In vivo modulation of Nogo-B attenuates neointima formation

Angelika B Kritz, Jun Yu, Paulette L Wright, Song Wan, Sarah J George, Crawford Halliday, Ning Kang, William C Sessa, Andrew H Baker

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1798-804
Number of pages7
JournalMolecular Therapy
Volume16
Issue number11
DOIs
Publication statusPublished - Nov 2008

Keywords

  • Adenoviridae
  • Animals
  • Carotid Arteries
  • Cell Proliferation
  • Cells, Cultured
  • Chemotaxis
  • Constriction, Pathologic
  • Disease Models, Animal
  • Femoral Artery
  • Gene Transfer Techniques
  • Genetic Vectors
  • Graft Occlusion, Vascular
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular
  • Myelin Proteins
  • Saphenous Vein
  • Swine
  • Tunica Intima
  • Tunica Media

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