Document Detail

Oligonucleotide microarrays reveal regulated genes related to inward arterial remodeling induced by urokinase plasminogen activator.
MedLine Citation:
PMID:  18812699     Owner:  NLM     Status:  MEDLINE    
Accumulating evidence suggests that urokinase plasminogen activator (uPA) is involved in vascular remodeling and lumen stenosis after angioplasty and stenting. We have shown previously that increased uPA expression greatly promotes neointima formation and inward arterial remodeling after balloon injury. To evaluate the role of inflammation in early mechanisms responsible for inward arterial remodeling induced by uPA and elucidate the mechanisms of remodeling, we characterized changes in the expression profiles of 8,799 genes in injured rat carotid arteries 1 and 4 days after recombinant uPA treatment compared to vehicle. We used a standard model of the balloon catheter injury of the rat carotid followed by periadventitial application to the injured vessel of either uPA dissolved in Pluronic gel, or plain gel. Vessels were harvested and analyzed by immunohistochemistry, morphometry, microarray gene expression profiling and quantitative RT-PCR. Periadventitial application of uPA significantly reduced lumen size and vessel area encompassed by the external elastic lamina at both 1 and 4 days after treatment. Inflammatory cells accumulated in the arterial adventitia at both 1 and 4 days after uPA treatment. On the 4th day, increases in the areas and arterial cell numbers of all arterial layers were found. Among 79 differentially expressed known genes 1 day after uPA application, 12 proinflammatory genes, including TNF-alpha and TACE, and 15 genes related to mitochondrial metabolism and oxidative stress regulation were identified. Four days after injury in uPA-treated arteries, 3 proinflammatory and 2 oxidation-related genes were differentially expressed. We conclude that uPA likely promotes inward arterial remodeling by regulating oxidative stress and inflammation after arterial injury.
Olga Plekhanova; Bradford C Berk; Pavel Bashtrykov; Andrew I Brooks; Vsevolod Tkachuk; Yelena Parfyonova
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-09-24
Journal Detail:
Title:  Journal of vascular research     Volume:  46     ISSN:  1423-0135     ISO Abbreviation:  J. Vasc. Res.     Publication Date:  2009  
Date Detail:
Created Date:  2009-04-24     Completed Date:  2009-05-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  177-87     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2008 S. Karger AG, Basel.
Molecular Endocrinology Laboratory, Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
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MeSH Terms
Arteries / drug effects*,  pathology
Gene Expression Profiling
Gene Expression Regulation / drug effects
Interleukin-1beta / genetics,  physiology
Oligonucleotide Array Sequence Analysis / methods*
Oxidative Stress
Polymerase Chain Reaction
Proliferating Cell Nuclear Antigen / analysis
Rats, Inbred WKY
Tumor Necrosis Factor-alpha / genetics,  physiology
Urokinase-Type Plasminogen Activator / toxicity*
Grant Support
Reg. No./Substance:
0/Interleukin-1beta; 0/Proliferating Cell Nuclear Antigen; 0/Tumor Necrosis Factor-alpha; EC Plasminogen Activator

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