Document Detail


Factor Xa inhibition by immobilized recombinant tissue factor pathway inhibitor.
MedLine Citation:
PMID:  17094640     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The recombinant form of the endogenous anticoagulant, tissue factor pathway inhibitor (rTFPI), is a potent inhibitor of Factor Xa (FXa) and the tissue factor-factor VIIa (TF:VIIa) complex. Surface-immobilized rTFPI reduces the thrombogenicity and intimal hyperplasia associated with synthetic vascular grafts in animal models and specifically reduces fibrin deposition on collagen-impregnated Dacron grafts from native blood in an in vitro flow model. The FXa inhibitory capacity of rTFPI in the bulk phase has been demonstrated in static systems and immobilized rTFPI reduces fibrin deposition in whole blood in vitro and animal studies; however, the specific mode of this anticoagulation has not been studied. Therefore, a comparison was made between the FXa binding capacity of two forms of immobilized rTFPI, i.e., passively adsorbed and covalently bound. The rTFPI-coated surfaces were evaluated using a parallel-plate flow reactor and comparing the amount of FXa exiting the flow chamber after exposure to an rTFPI-coated versus an uncoated plate. The results demonstrate that adsorbed rTFPI exhibits increased binding capacity (1.5-3.6 times) the expected stoichiometry via interactions with the C-terminus, whereas covalently-bound rTFPI interacts with FXa in a 1:1 stoichiometry. Thus, the results imply that specific FXa inhibition is a key component of the anticoagulant effect of rTFPI-coated surfaces and that passive adsorption of rTFPI to glass surfaces produces a more effective coating than covalent binding of rTFPI.
Authors:
Amito Chandiwal; Fowzia Shahreen Zaman; Alan E Mast; Connie L Hall
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biomaterials science. Polymer edition     Volume:  17     ISSN:  0920-5063     ISO Abbreviation:  J Biomater Sci Polym Ed     Publication Date:  2006  
Date Detail:
Created Date:  2006-11-10     Completed Date:  2006-12-05     Revised Date:  2008-02-20    
Medline Journal Info:
Nlm Unique ID:  9007393     Medline TA:  J Biomater Sci Polym Ed     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1025-37     Citation Subset:  IM    
Affiliation:
Department of Biomedical Engineering, The University of Memphis, Memphis, TN, USA.
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MeSH Terms
Descriptor/Qualifier:
Adsorption
Blood Vessel Prosthesis
Factor Xa / antagonists & inhibitors*,  chemistry*,  physiology
Humans
Kinetics
Lipoproteins / chemistry*,  pharmacology
Recombinant Proteins / pharmacology
Grant Support
ID/Acronym/Agency:
HL68835/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lipoproteins; 0/Recombinant Proteins; 0/lipoprotein-associated coagulation inhibitor; EC 3.4.21.6/Factor Xa

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


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