| COX-1(+/-) COX-2(-/-) genotype in mice is associated with shortened time to carotid artery occlusion through increased PAI-1. | |
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MedLine Citation:
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PMID: 21138526 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Summary. Background: We found a high incidence of thrombotic deaths in COX-1(+/-) COX-2(-/-) mice and sought to define the mechanism of these events. The cyclooxygenase products thromboxane A(2) and prostacyclin are important in the regulation of coagulation but their role in fibrinolysis is largely unexplored. PAI-1 blocks fibrinolysis by inhibiting plasminogen activator. Aim: Our objective was to explain the mechanism of increased thrombosis associated with the COX-1(+/-) COX-2(-/-) genotype. Methods: Carotid artery occlusion times were measured after photochemical injury. PAI-1 levels were measured in the plasma by ELISA. PAI-1 levels in the aorta were measured by RT-PCR and Western blotting. Urinary metabolites of Thromboxane A(2) and prostacyclin were measured by ELISA. Results: The COX-1(+/-) COX-2(-/-) genotype is associated with a decreased time to occlusion in the carotid artery thrombosis model (30 ± 5 minutes vs 60 ± minutes in wild type, p<.001). The COX-1(-/-) COX-2(+/+) , COX-1(+/-) COX-2(+/-) and COX-1(+/-) COX-2(+/+) all had occlusion times similar to wild type. COX-1(+/+) COX-2(-/-) had a prolonged occlusion time. COX-1(+/-) COX-2(-/-) had increased PAI-1 levels in the plasma and aorta and with a prolonged euglobulin lysis time (37.4 ± 10.2 hours vs 15.6 ± 9.8 hours in wild type, p<.004). The decreased time to occlusion in the COX-1(+/-) COX2(-/-) mice was normalized by an inhibitory antibody to PAI-1 whereas the antibody had no effect on the time to occlusion in wild type mice. Conclusion: The COX-1(+/-) COX-2(-/-) genotype is associated with a shortened time to occlusion in the carotid thrombosis model and the shortened time to occlusion is mediated through increased PAI-1 levels resulting in decreased fibrinolysis. |
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Authors:
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T E Riehl; L He; L Zheng; S Greco; D M Tollefsen; W F Stenson |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of thrombosis and haemostasis : JTH Volume: 9 ISSN: 1538-7836 ISO Abbreviation: J. Thromb. Haemost. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-28 Completed Date: - Revised Date: - |
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: 350-60 Citation Subset: IM |
Copyright Information:
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© 2011 International Society on Thrombosis and Haemostasis. |
Affiliation:
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Divisions of Gastroenterology Hematology, Department of Medicine Division of Comparative Medicine, Washington University School of Medicine, St Louis, MO, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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