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Fibrinolytic Resistance and Prothrombotic Phenotype is Altered in Mice Lacking α(1,3)‐Fucosyltransferase‐IV and – VII
Author(s) -
Wang Huili,
Mackey Lantz,
Rose Jason,
Homeister Jonathon W
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.832.1
Subject(s) - fibrinolysis , fibrinogen , chemistry , plasminogen activator , medicine , endocrinology , platelet , in vivo , immunology , biochemistry , biology , microbiology and biotechnology
Mice deficient in α(1,3)‐fucosyltransferase type‐IV and ‐VII (DKO) lack selectin‐type leukocyte adhesion molecule ligand activity, and show a prothrombotic phenotype in a model of carotid artery injury that is associated with enhanced platelet aggregation. We sought to confirm the prothrombotic phenotype in a second experimental model, and examine whether it was in part due to increased procoagulant activity. The phenotype was examined using an in vivo model of collagen‐epinephrine‐induced pulmonary thromboembolism. Plasma procoagulant activity was assessed by calibrated automated thrombography (CAT), fibrinogen ELISA, and a tissue‐type plasminogen activator (tPA)‐ induced thrombolysis assay. DKO mice had more pulmonary thromboemboli and a higher mortality rate than wild‐type (WT) controls or mice deficient in P‐selectin glycoprotein ligand‐1. Thrombin generation in DKO mice was not different from WT mice, but DKO mice had a 30% higher plasma fibrinogen concentration. tPA‐dependent fibrinolysis, measured by release of labeled fibrinogen degradation products, was reduced in DKO whole blood clot compared to wild‐type clot. WT clot dry weight after lysis was reduced 38%, but DKO clot weight was reduced only 9%. These data confirm the selectin‐independent prothrombotic phenotype of DKO mice and suggest that it is due in part to increased plasma fibrinogen and decreased fibrinolysis.