| Causal relationship between hyperfibrinogenemia, thrombosis, and resistance to thrombolysis in mice. | |
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MedLine Citation:
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PMID: 21355090 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epidemiologic studies have correlated elevated plasma fibrinogen (hyperfibrinogenemia) with risk of cardiovascular disease and arterial and venous thrombosis. However, it is unknown whether hyperfibrinogenemia is merely a biomarker of the proinflammatory disease state or is a causative mechanism in the etiology. We raised plasma fibrinogen levels in mice via intravenous infusion and induced thrombosis by ferric chloride application to the carotid artery (high shear) or saphenous vein (lower shear); hyperfibrinogenemia significantly shortened the time to occlusion in both models. Using immunohistochemistry, turbidity, confocal microscopy, and elastometry of clots produced in cell and tissue factor-initiated models of thrombosis, we show that hyperfibrinogenemia increased thrombus fibrin content, promoted faster fibrin formation, and increased fibrin network density, strength, and stability. Hyperfibrinogenemia also increased thrombus resistance to tenecteplase-induced thrombolysis in vivo. These data indicate that hyperfibrinogenemia directly promotes thrombosis and thrombolysis resistance and does so via enhanced fibrin formation and stability. These findings strongly suggest a causative role for hyperfibrinogenemia in acute thrombosis and have significant implications for thrombolytic therapy. Plasma fibrinogen levels may be used to identify patients at risk for thrombosis and inform thrombolytic administration for treating acute thrombosis/thromboembolism. |
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Authors:
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Kellie R Machlus; Jessica C Cardenas; Frank C Church; Alisa S Wolberg |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-02-25 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-06 Completed Date: 2011-07-05 Revised Date: 2012-05-08 |
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: 4953-63 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carotid Artery Thrombosis / blood, drug therapy, etiology Chlorides / toxicity Disease Models, Animal Drug Resistance Ferric Compounds / toxicity Fibrinogen / administration & dosage, metabolism* Fibrinolytic Agents / pharmacology* Humans Male Mice Mice, Inbred C57BL Platelet Aggregation Risk Factors Saphenous Vein / drug effects, injuries Thrombolytic Therapy Thrombosis / blood*, drug therapy*, etiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL094740-04/HL/NHLBI NIH HHS; R01HL094740/HL/NHLBI NIH HHS; R21AG031068/AG/NIA NIH HHS; T32 HL697668/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chlorides; 0/Ferric Compounds; 0/Fibrinolytic Agents; 7705-08-0/ferric chloride; 9001-32-5/Fibrinogen |
| Comments/Corrections | |
Comment In:
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Blood. 2011 May 5;117(18):4687-8
[PMID:
21546470
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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