Document Detail


Adenovirus-mediated local expression of human tissue factor pathway inhibitor eliminates shear stress-induced recurrent thrombosis in the injured carotid artery of the rabbit.
MedLine Citation:
PMID:  10381897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The main cause of acute coronary syndrome may be recurrent thrombosis, which is initiated by the activation of the extrinsic coagulation pathway. Tissue factor (TF) pathway inhibitor (TFPI) efficiently inhibits an early step in this pathway by the formation of a complex with factor VIIa, TF, and factor Xa. We determined whether local TFPI gene transfer can inhibit thrombosis in an injured artery without inducing systemic side effects. Balloon-injured rabbit carotid arteries were infected with an adenoviral vector that expressed either human TFPI (AdCATFPI) or bacterial beta-galactosidase (AdCALacZ). Two to 6 days after gene transfer, thrombosis was induced by the production of constant stenosis of the artery, and blood flow was measured continuously with an electromagnetic flow probe. A cyclic flow variation, which is thought to reflect the recurrent formation and dislodgment of mural thrombi, was observed in all AdCALacZ-infected arteries as well as in saline-infused arteries. In contrast, no cyclic flow variation was detectable in AdCATFPI-transfected arteries, even in the presence of epinephrine (1 microg. kg-1. min-1 infusion). Prothrombin time, activated partial thromboplastin time, and the ex vivo platelet aggregation induced by either adenosine diphosphate or collagen were unaltered in AdCATFPI-infected rabbits. We found that in vivo TFPI gene transfer into an injured artery completely inhibits the recurrent thrombosis induced by shear stress even in the presence of catecholamine, without affecting systemic coagulation status. Adenovirus-mediated local expression of TFPI may have the potential for the treatment of human thrombosis.
Authors:
T Nishida; H Ueno; N Atsuchi; R Kawano; Y Asada; Y Nakahara; Y i Kamikubo; A Takeshita; H Yasui
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation research     Volume:  84     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-07-16     Completed Date:  1999-07-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1446-52     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Surgery, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae*
Angioplasty, Balloon / adverse effects
Animals
Blood Flow Velocity
Blood Pressure
COS Cells
Carotid Arteries / chemistry,  physiopathology
Carotid Artery Injuries*
Gene Transfer Techniques*
Humans
Male
Partial Thromboplastin Time
Platelet Aggregation
Prothrombin Time
Rabbits
Recurrence
Stress, Mechanical
Thromboplastin / genetics*,  secretion
Thrombosis / etiology,  therapy*
Chemical
Reg. No./Substance:
9035-58-9/Thromboplastin

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


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