The effects of pharmacological PAI-1 inhibition on thrombus formation and neointima formation after arterial injury. 2008

Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
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

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.

UI MeSH Term Description Entries
D006965 Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells. Hyperplasias
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003331 Coronary Vessels The veins and arteries of the HEART. Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005340 Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. Coagulation Factor I,Factor I,Blood Coagulation Factor I,gamma-Fibrinogen,Factor I, Coagulation,gamma Fibrinogen
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013927 Thrombosis Formation and development of a thrombus or blood clot in BLOOD VESSELS. Atherothrombosis,Thrombus,Blood Clot,Blood Clots,Thromboses
D015906 Angioplasty, Balloon, Coronary Dilation of an occluded coronary artery (or arteries) by means of a balloon catheter to restore myocardial blood supply. Angioplasty, Coronary Balloon,Angioplasty, Transluminal, Percutaneous Coronary,Coronary Angioplasty, Transluminal Balloon,Percutaneous Transluminal Coronary Angioplasty,Balloon Dilation, Coronary Artery,Transluminal Coronary Balloon Dilation,Angioplasties, Coronary Balloon,Balloon Angioplasties, Coronary,Balloon Angioplasty, Coronary,Coronary Balloon Angioplasties,Coronary Balloon Angioplasty

Related Publications

Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
January 2001, Annals of the New York Academy of Sciences,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
January 2004, Journal of thrombosis and haemostasis : JTH,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
December 1996, Circulation,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
April 2014, Atherosclerosis,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
January 2004, Journal of vascular research,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
January 1999, Circulation research,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
May 2006, Diabetes, obesity & metabolism,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
November 2009, Circulation research,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
October 2003, Journal of cardiovascular pharmacology,
Jun-ichi Suzuki, and Masahito Ogawa, and Susumu Muto, and Yoichi Yamaguchi, and Akiko Itai, and Mitsuaki Isobe
June 2017, Thrombosis and haemostasis,
Copied contents to your clipboard!