Document Detail

The effects of pharmacological PAI-1 inhibition on thrombus formation and neointima formation after arterial injury.
MedLine Citation:
PMID:  18554148     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Plasminogen activator inhibitor (PAI)-1 plays a role in neointimal formation after percutaneous coronary intervention (PCI), the effect of overexpression or lack of PAI-1 is controversial. Murine arterial injury models develop neointimal hyperplasia similar to that observed in clinical coronary arterial restenosis after PCI. METHODS AND RESULTS: To clarify the role of PAI-1 in thrombus formation and neointimal formation after arterial injury, we used a specific PAI-1 inhibitor (IMD-1622) in a rat aorta-vein shunt model and a mouse arterial injury model. While the non-treated shunt model showed massive thrombus formation, IMD-1622 administration suppressed this. Injured arteries with vehicles showed significant neointimal formation with enhancement of adhesion molecules, fibrinogen accumulation and cell proliferation on day 28 after injury. However, intimal thickening and expression of these factors were suppressed in PAI-1 recipients. CONCLUSION: A specific PAI-1 inhibitor prevents thrombus formation and arterial neointimal formation after arterial injury. Thus, PAI-1 plays a critical role in arterial remodeling after mechanical injury. PAI-1 regulation may be useful to prevent thrombus and neointimal formation after PCI.
Jun-ichi Suzuki; Masahito Ogawa; Susumu Muto; Yoichi Yamaguchi; Akiko Itai; Mitsuaki Isobe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  12     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-16     Completed Date:  2008-08-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  783-94     Citation Subset:  IM    
Tokyo Medical and Dental University, Graduate School of Medicine, Department of Cardiovascular Medicine, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
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MeSH Terms
Angioplasty, Transluminal, Percutaneous Coronary*
Cell Proliferation / drug effects
Coronary Restenosis / prevention & control
Coronary Vessels / drug effects,  pathology
Disease Models, Animal
Fibrinogen / metabolism
Gene Expression Regulation / drug effects
Hyperplasia / prevention & control
Mice, Inbred C57BL
Plasminogen Activator Inhibitor 1 / metabolism*
Rats, Sprague-Dawley
Thiazolidinediones / pharmacology*
Thrombosis / physiopathology*,  prevention & control
Tunica Intima / drug effects*,  pathology
Reg. No./Substance:
0/3-(3,4-dichlorobenzyl)-5-(3,4,5-trihydroxybenzylidene)thiazolidine-2,4-dione; 0/Plasminogen Activator Inhibitor 1; 0/Thiazolidinediones; 9001-32-5/Fibrinogen

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