| Fibrinogen gamma-chain splice variant gamma' alters fibrin formation and structure. | |
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MedLine Citation:
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PMID: 12663453 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Amy V Cooper; Kristina F Standeven; Robert A S Ariëns |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-03-27 |
Journal Detail:
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Title: Blood Volume: 102 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2003 Jul |
Date Detail:
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Created Date: 2003-07-01 Completed Date: 2003-09-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 535-40 Citation Subset: AIM; IM |
Affiliation:
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Academic Unit of Molecular Vascular Medicine, University of Leeds, Leeds General Infirmary, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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