| Plasminogen activator inhibitor-1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice. | |
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MedLine Citation:
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PMID: 11157725 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The origin and contribution of plasminogen activator inhibitor-1 (PAI-1) and its cofactor vitronectin (VN) to arterial thrombosis/thrombolysis in vivo is controversial. METHODS AND RESULTS: Ferric chloride was used to induce carotid artery injury in 97 wild-type (WT), 84 PAI-1-/-, and 84 VN-/- mice. Complete thrombotic occlusion was observed in 70% of PAI-1-/- mice versus 92% of WT (P:<0.001) and 87% of VN-/- (P:=0.015) mice. In vessels that occluded, mean times to occlusion were significantly longer in PAI-1-/- than in WT or VN-/- mice. The initial thrombotic response of VN-/- mice was similar to that of WT mice, but their thrombi were unstable and frequently embolized. As a result, the patency rate of carotid vessels 30 minutes after injury was as high in VN-/- mice (36%) as in PAI-1-/- mice (which demonstrate progressive thrombolysis) and significantly higher than that of WT mice (12%; P:=0.013). Histochemical and reverse transcription-polymerase chain reaction studies revealed an early upregulation of PAI-1 mRNA and protein expression in the thrombus and the vessel wall, which persisted for >/=1 week. VN protein also accumulated after injury, but VN mRNA levels remained low at all times. CONCLUSIONS: PAI-1 and VN participate in the thrombotic response to arterial injury by preventing premature thrombus dissolution and embolization. The accumulation of PAI-1 in the thrombus/vessel wall after injury may result, at least in part, from local synthesis, whereas the VN protein appears to be derived from plasma. |
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Authors:
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S Konstantinides; K Schäfer; T Thinnes; D J Loskutoff |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 103 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2001 Jan |
Date Detail:
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Created Date: 2001-02-22 Completed Date: 2001-04-26 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 576-83 Citation Subset: IM |
Affiliation:
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Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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analysis Animals Blood Circulation Carotid Arteries / metabolism, pathology, physiopathology* Carotid Artery Injuries / etiology, genetics, physiopathology Female Ferric Compounds / administration & dosage Gene Expression Genotype Immunohistochemistry In Situ Hybridization Male Mice Mice, Inbred C57BL Mice, Mutant Strains Muscle, Smooth, Vascular / chemistry, cytology Plasminogen Activator Inhibitor 1 / genetics, physiology* RNA, Messenger / genetics, metabolism Thrombosis / physiopathology* Time Factors Vimentin / analysis Vitronectin / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL-31950/HL/NHLBI NIH HHS; HL-47819/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Ferric Compounds; 0/Plasminogen Activator Inhibitor 1; 0/RNA, Messenger; 0/Vimentin; 0/Vitronectin; 7705-08-0/ferric chloride |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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