Document Detail


Fibrinogen gamma-chain splice variant gamma' alters fibrin formation and structure.
MedLine Citation:
PMID:  12663453     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibrinogen gammaA/gamma' results from alternative splicing of mRNA. This variant, which constitutes approximately 8% to 15% of plasma fibrinogen, contains FXIII and thrombin binding sites. Our objective was to investigate whether gammaA/gamma' differs in fibrin formation and structure from the more common variant gammaA/gammaA. Both variants were separated and purified by anion-exchange chromatography. Fibrin formation and clot structure of the variants and unfractionated fibrinogen were investigated by turbidity and scanning electron microscopy (SEM). Thrombin cleavage of fibrinopeptides was analyzed by high-performance liquid chromatography (HPLC). Turbidity analysis showed significantly altered polymerization rates and overall fiber thickness in gammaA/gamma' clots compared with gammaA/gammaA and unfractionated fibrinogen. This finding was consistent with a range of thrombin concentrations. HPLC demonstrated reduced rates of fibrinopeptide B (FpB) release from gammaA/gamma' fibrinogen compared with gammaA/gammaA. Delayed FpB release was associated with delayed lateral aggregation of protofibrils and significant differences were found on SEM, with gammaA/gamma' clots consisting of smaller diameter fibers and increased numbers of branch points compared with both gammaA/gammaA and unfractionated fibrinogen. These results demonstrate that the gammaA/gamma' splice variant of fibrinogen directly alters fibrin formation and structure, which may help to explain the increased thrombotic risk associated with this variant.
Authors:
Amy V Cooper; Kristina F Standeven; Robert A S Ariëns
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-03-27
Journal Detail:
Title:  Blood     Volume:  102     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-07-01     Completed Date:  2003-09-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  535-40     Citation Subset:  AIM; IM    
Affiliation:
Academic Unit of Molecular Vascular Medicine, University of Leeds, Leeds General Infirmary, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing*
Blood Coagulation
Chromatography, High Pressure Liquid
Fibrin / chemistry*
Fibrinogen / chemistry*,  genetics,  ultrastructure
Fibrinopeptide B / metabolism
Humans
Microscopy, Electron, Scanning
Nephelometry and Turbidimetry
Protein Isoforms / chemistry,  genetics
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Protein Isoforms; 36204-23-6/Fibrinopeptide B; 9001-31-4/Fibrin; 9001-32-5/Fibrinogen

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


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