Document Detail

Intramural delivery of bortezomib inhibits restenosis following arterial injury.
MedLine Citation:
PMID:  22090177     Owner:  NLM     Status:  MEDLINE    
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.
X Gong; Y Zhou
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  VASA. Zeitschrift für Gefässkrankheiten     Volume:  40     ISSN:  0301-1526     ISO Abbreviation:  VASA     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2012-01-31     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  0317051     Medline TA:  Vasa     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  449-52     Citation Subset:  IM    
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MeSH Terms
Boronic Acids / pharmacology*
Constriction, Pathologic / pathology
Cyclin-Dependent Kinase Inhibitor p27 / analysis
Down-Regulation / drug effects
Iliac Artery / drug effects*,  injuries*,  pathology
Immunoenzyme Techniques
Muscle, Smooth, Vascular / drug effects,  pathology
NF-kappa B / analysis
Neointima / pathology*
Protease Inhibitors / pharmacology*
Proteasome Inhibitors*
Pyrazines / pharmacology*
Reg. No./Substance:
0/Boronic Acids; 0/NF-kappa B; 0/Protease Inhibitors; 0/Proteasome Inhibitors; 0/Pyrazines; 0/bortezomib; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27
Comment In:
Vasa. 2011 Nov;40(6):425-6   [PMID:  22191123 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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