title: Intramural delivery of bortezomib inhibits restenosis following arterial injury.
abstract: BACKGROUND
  Several studies have demonstrated that the proteasome inhibitors prevent restenosis following arterial injury. The proteasome inhibitor bortezomib shows anti-inflammatory and antiproliferative effects. Here, we evaluate the efficacy of bortezomib in inhibiting the restenosis following arterial injury and the effect on nuclear factor kappa B (NF-kappaB) and p27.
  
  
  METHODS
  An injured iliac artery rabbit model was established by balloon over-stretching. Rabbits were intramurally infused with bortezomib or normal saline by a transport coronary dilatation catheter in the bortezomib (n = 20) or control (n = 20) groups, respectively, and they were sacrificed on the 7th or 21th day following the arterial injury. Neointimal area was measured by computer analysis of photomicrographs, while expression of NF-kappaB and of p27 on day 7 were evaluated by Western blotting and immunohistochemistry, respectively.
  
  
  RESULTS
  Expression of p27 (56.10 ± 3.03% vs. 10.24 ± 0.60%, p < 0.05) was significantly higher while that of NF-kappaB (0.44 ± 0.02 vs. 0.70 ± 0.03, p < 0.05) was significantly lower in the bortezomib group than in control group on day 7 after arterial injury. Neointimal formation was significantly lower in the bortezomib group on day 21 after arterial injury (0.67 ± 0.03 vs. 1.30 ± 0.05 intima/media ratio, p < 0.05).
  
  
  CONCLUSIONS
  Intramural delivery of bortezomib reduces neointimal formation, possibly via a mechanism involving upregulation of the p27 and downregulation of the NF-kappaB. Bortezomib therefore may be an alternative therapeutic approach for preventing restenosis.
authors.affiliation: Department of Cardiology, Capital Medical University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Gong
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D003251:Constriction, Pathologic / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D015536:Down-Regulation / Q000187:drug effects; D007083:Iliac Artery / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D016328:NF-kappa B / Q000032:analysis; D058426:Neointima / Q000473:pathology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D001897:Boronic Acids; D016328:NF-kappa B; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000069286:Bortezomib