Document Detail

The fibrinogen γA/γ' isoform does not promote acute arterial thrombosis in mice.
MedLine Citation:
PMID:  24916154     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Elevated plasma fibrinogen is associated with arterial thrombosis in humans and promotes thrombosis in mice by increasing fibrin formation and thrombus fibrin content. Fibrinogen is composed of six polypeptide chains: (Aα, Bβ, and γ)2. Alternative splicing of the γ chain leads to a dominant form (γA/γA) and a minor species (γA/γ'). Epidemiological studies have detected elevated γA/γ' fibrinogen in patients with arterial thrombosis, suggesting that this isoform promotes thrombosis. However, in vitro data show that γA/γ' is anticoagulant due to its ability to sequester thrombin and suggest its expression is upregulated in response to inflammatory processes.
OBJECTIVE: To determine whether γA/γ' fibrinogen is prothrombotic in vivo.
METHODS: We separated γA/γA and γA/γ' fibrinogen from human plasma-purified fibrinogen and determined the effects on in vitro plasma clot formation and on in vivo thrombus formation and circulating thrombin-antithrombin complexes in mice.
RESULTS AND CONCLUSIONS: Both γA/γA and γA/γ' fibrinogen were cleaved by murine and human thrombin and were incorporated into murine and human clots. When γA/γA or γA/γ' was spiked into plasma, γA/γA increased the fibrin formation rate to a greater extent than γA/γ'. In mice, compared to controls, γA/γA infusion shortened the time to carotid artery occlusion, whereas γA/γ' infusion did not. Additionally, γA/γ' infusion led to lower levels of plasma thrombin-antithrombin complexes following arterial injury, whereas γA/γA infusion did not. These data suggest that γA/γ' binds thrombin in vivo and decreases prothrombotic activity. Together, these findings indicate that elevated levels of γA/γA fibrinogen promote arterial thrombosis in vivo, whereas γA/γ' does not.
B L Walton; T M Getz; W Bergmeier; F-C Lin; S Uitte de Willige; A S Wolberg
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  12     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-06-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  680-9     Citation Subset:  IM    
Copyright Information:
© 2014 International Society on Thrombosis and Haemostasis.
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