| Thrombogenesis with continuous blood flow in the inferior vena cava. A novel mouse model. | |
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MedLine Citation:
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PMID: 20589322 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several rodent models have been used to study deep venous thrombosis (DVT). However, a model that generates consistent venous thrombi in the presence of continuous blood flow, to evaluate therapeutic agents for DVT, is not available. Mice used in the present study were wild-type C57BL/6 (WT), plasminogen activator inhibitor-1 (PAI-1) knock out (KO) and Delta Cytoplasmic Tail (DCT). An electrolytic inferior vena cava (IVC) model (EIM) was used. A 25G stainless-steel needle, attached to a silver coated copper wire electrode (anode), was inserted into the exposed caudal IVC. Another electrode (cathode) was placed subcutaneously. A current of 250 muAmps over 15 minutes was applied. Ultrasound imaging was used to demonstrate the presence of IVC blood flow. Analyses included measurement of plasma soluble P-selectin (sP-Sel), thrombus weight (TW), vein wall morphometrics, P-selectin and Von Willebrand factor (vWF) staining, transmission electron microscopy (TEM), scanning electron microscopy (SEM); and the effect of enoxaparin on TW was evaluated. A current of 250 muAmps over 15 minutes consistently promoted thrombus formation in the IVC. Plasma sP-Sel was decreased in PAI-1 KO and increased in DCT vs. WT (WT/PAI-1: p=0.003, WT/DCT: p=0.0002). Endothelial activation was demonstrated by SEM, TEM, P-selectin and vWF immunohistochemistry and confirmed by inflammatory cell counts. Ultrasound imaging demonstrated thrombus formation in the presence of blood flow. Enoxaparin significantly reduced the thrombus size by 61% in this model. This EIM closely mimics clinical venous disease and can be used to study endothelial cell activation, leukocyte migration, thrombogenesis and therapeutic applications in the presence of blood flow. |
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Authors:
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José A Diaz; Angela E Hawley; Christine M Alvarado; Alexandra M Berguer; Nichole K Baker; Shirley K Wrobleski; Thomas W Wakefield; Benedict R Lucchesi; Daniel D Myers |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-29 |
Journal Detail:
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Title: Thrombosis and haemostasis Volume: 104 ISSN: 0340-6245 ISO Abbreviation: Thromb. Haemost. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-12-02 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 7608063 Medline TA: Thromb Haemost Country: Germany |
Other Details:
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Languages: eng Pagination: 366-75 Citation Subset: IM |
Affiliation:
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Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, Michigan 48109-0654, USA. josediaz@med.umich.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Coagulation* / genetics Disease Models, Animal* Electrolysis Endothelial Cells / metabolism Enoxaparin / pharmacology Fibrinolytic Agents / pharmacology Male Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Electron, Scanning Microscopy, Electron, Transmission Neutrophil Infiltration P-Selectin / blood, genetics Plasminogen Activator Inhibitor 1 / deficiency, genetics Regional Blood Flow Thrombophilia / blood, genetics, physiopathology Time Factors Ultrasonography, Doppler, Color Vena Cava, Inferior / injuries, metabolism, physiopathology*, ultrasonography, ultrastructure Venous Thrombosis / blood, diagnosis, genetics, physiopathology*, prevention & control von Willebrand Factor / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1 K01 HL080962-01A2/HL/NHLBI NIH HHS; 1P01HL089407-01A1/HL/NHLBI NIH HHS; P01 HL089407-01A1/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enoxaparin; 0/Fibrinolytic Agents; 0/P-Selectin; 0/Plasminogen Activator Inhibitor 1; 0/von Willebrand Factor |
| Comments/Corrections | |
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