The effects of pharmacological PAI-1 inhibition on thrombus formation and neointima formation after arterial injury.
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.


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.


CONCLUSIONS
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.
Tokyo Medical and Dental University, Graduate School of Medicine, Department of Cardiovascular Medicine, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. jsuzuki.cvm@tmd.ac.jp
Jun-ichi
J
Suzuki
Masahito
M
Ogawa
Susumu
S
Muto
Yoichi
Y
Yamaguchi
Akiko
A
Itai
Mitsuaki
M
Isobe
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D023903:Coronary Restenosis / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology*; D013927:Thrombosis / Q000503:physiopathology* / Q000517:prevention & control; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
C530962:3-(3,4-dichlorobenzyl)-5-(3,4,5-trihydroxybenzylidene)thiazolidine-2,4-dione; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones; D005340:Fibrinogen