| Pregnancy-associated changes in the hemostatic system in wild-type and factor V Leiden mice. | |
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MedLine Citation:
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PMID: 19036061 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Pregnancy, oral contraceptive (OC)use and hormone replacement therapy (HRT) are established risk factors for venous thrombosis. Acquired resistance to activated protein C (APC) has been proposed to contribute to the increased thrombosis risk. Mouse models are often used for preclinical testing of newly developed hormone preparations. However, it is not known whether hormone-induced APC resistance is also observed in laboratory animals. OBJECTIVES: To investigate whether hormonal changes modulate APC resistance in mice, we used pregnant mice as a model of hormone-induced APC resistance. The effect of pregnancy on APC resistance was studied in wild-type and factor (F)V Leiden mice. METHODS: APC resistance was determined in mouse plasma using a thrombin generation-based APC resistance test. APC resistance determinants,i.e. prothrombin, FV, FX, antithrombin and protein S levels,and of tissue factor pathway inhibitor (TFPI) activity were evaluated in plasma from non-pregnant and pregnant mice. RESULTS: In contrast to humans, pregnancy induced a decrease in APC resistance in wild-type and in FV Leiden mice.Pregnant mice had higher levels of prothrombin, FV, FX,protein S and TFPI activity as compared with non-pregnant mice. CONCLUSIONS: Pregnancy causes a decrease in APC resistance in mice, which can be explained by the elevation of protein S levels and increased TFPI activity in plasma. Our findings show species specificity in the effects of pregnancy on the major determinants of the protein C system and suggest that protein S and TFPI play an important role in the development of pregnancy-induced APC resistance in humans. |
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Authors:
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S N Tchaikovski; B J M van Vlijmen; A C A Cleuren; M C L G D Thomassen; V Tchaikovski; G Tans; J Rosing |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of thrombosis and haemostasis : JTH Volume: 7 ISSN: 1538-7836 ISO Abbreviation: J. Thromb. Haemost. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-13 Completed Date: 2009-05-15 Revised Date: 2010-03-23 |
Medline Journal Info:
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Nlm Unique ID: 101170508 Medline TA: J Thromb Haemost Country: England |
Other Details:
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Languages: eng Pagination: 312-8 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Activated Protein C Resistance
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diagnosis,
etiology* Animals Biological Markers / blood Factor V* Female Hemostasis* Lipoproteins / blood* Mice Pregnancy Pregnancy Complications, Hematologic / blood Protein S / analysis* Species Specificity |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Lipoproteins; 0/Protein S; 0/factor V Leiden; 0/lipoprotein-associated coagulation inhibitor; 9001-24-5/Factor V |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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