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Publication : Selectins influence thrombosis in a mouse model of experimental deep venous thrombosis.

First Author  Myers D Jr Year  2002
Journal  J Surg Res Volume  108
Issue  2 Pages  212-21
PubMed ID  12505044 Mgi Jnum  J:103110
Mgi Id  MGI:3608468 Doi  10.1006/jsre.2002.6552
Citation  Myers D Jr, et al. (2002) Selectins influence thrombosis in a mouse model of experimental deep venous thrombosis. J Surg Res 108(2):212-21
abstractText  BACKGROUND: This study characterizes venous thrombosis in the mouse and examines the important role that the adhesion molecules P-selectin and E-selectin and the anti-inflammatory cytokine interleukin-10 (IL-10) play in the thrombotic process. MATERIALS AND METHODS: C57BL/6 (wild-type) mice in a natural history protocol (Phase I) and gene-targeted (KO) mice for P-selectin, E-selectin, P/E-selectin, and IL-10 in a follow-up protocol (Phase II) were studied. Inferior vena caval thrombosis was produced by ligation just below the renal veins, and mice were sacrificed and evaluated at various time points up to 12 days later. RESULTS: Phase I: A significant increase in neutrophils on day 2 and in monocytes on day 6 postthrombosis was found in ligated vs sham animals. An associated significant increase in vein wall P-selectin mRNA (6 h, day 2) and an increase in protein (6 h through day 6) were found, while E-selectin mRNA was significantly increased (day 2 through day 6), with a smaller increase in E-selectin protein. IL-10 mRNA increased significantly later (day 2 through day 9), with the values increasing progressively. A positive correlation existed (r = 0.77) between neutrophils and thrombosis at day 2. PHASE II: The E-selectin and P/E-selectin double-KO mice showed the least thrombus at day 2 vs wild-type clotted mice, P < 0.01. Additionally, P/E-KO mice demonstrated the lowest inflammatory cell extravasation into the vein wall at day 2. CONCLUSIONS: This study demonstrates an acute to chronic inflammatory response in the vein wall associated with venous thrombosis. Inhibition of selectins decreased thrombus formation.
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