Document Detail


The role of c-jun in PDTC-sensitive flow-dependent restenosis after angioplasty and stenting.
MedLine Citation:
PMID:  17194461     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Restenosis after balloon angioplasty and stenting is exacerbated by low flow. Flow-dependent restenosis after angioplasty but not stenting is prevented by the antioxidant pyrrolidine dithiocarbamate (PDTC). c-jun may play a role in these events as AP-1 activity is both flow and redox sensitive. Carotid arteries of cholesterol fed rabbits underwent stenting or balloon injury in the presence of low or normal flow. c-jun mRNA expression was enhanced by low flow and injury (stent>balloon) and inhibited by the antioxidant PDTC irrespective of the injury type. The effect of locally delivered DZ13 (a DNAzyme specific for c-jun) or scrambled DZ13 (inactive DNAzyme) was assessed by histomorphometry at 28 days. Low flow significantly increased intimal hyperplasia in B and S relative to normal flow (P<0.05). The active DNAzyme DZ13 markedly reduced intimal hyperplasia (P<0.001) and increased lumen size (P<0.05) in balloon-injured but not in stented segments, and abrogated the effect of low flow on restenosis after angioplasty, similar to the morphological effects of PDTC. We conclude that c-jun expression is enhanced by low flow and by injury (stent>balloon) and markedly attenuated by PDTC, and that c-jun is an important mediator of flow-dependent restenosis in balloon-injured but not stented vessels.
Authors:
Melanie Murrell; Levon Khachigian; Michael R Ward
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-27
Journal Detail:
Title:  Atherosclerosis     Volume:  194     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-09     Completed Date:  2007-12-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  364-71     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Royal North Shore Hospital, Australia.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Balloon / adverse effects
Animals
Antioxidants / pharmacology
Blood Flow Velocity / physiology*
Carotid Artery, Common / physiopathology*
Carotid Stenosis / physiopathology*
Coronary Restenosis / physiopathology
DNA, Catalytic / pharmacology
Diet, Atherogenic
Disease Models, Animal
Gene Expression Regulation
Genes, jun / drug effects
Proto-Oncogene Proteins c-jun / drug effects,  genetics,  metabolism*
Pyrrolidines / pharmacology
Rabbits
Stents / adverse effects
Thiocarbamates / pharmacology
Chemical
Reg. No./Substance:
0/Antioxidants; 0/DNA, Catalytic; 0/Dz13 DNAzyme; 0/Proto-Oncogene Proteins c-jun; 0/Pyrrolidines; 0/Thiocarbamates; 25769-03-3/pyrrolidine dithiocarbamic acid

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


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