homeostasis/metabolism
N |
• platelets aggregate normally in response to collagen or thrombin
• no alterations in prothrombin time or activated partial thromboplastin time are observed, indicating normal coagulation
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• mice show impaired histamine-induced release of endothelial von Willebrand factor (vWF), with plasma vWF levels reduced by ~50% at 30 min after i.p. histamine injection
• however, basal plasma vWF levels are normal
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• in a tail bleed assay, most mice lose on average 6-fold more blood than wild-type controls, indicating impaired hemostasis
• some mice do not bleed excessively, suggesting that the bleeding phenotype is variable
• impaired hemostasis is due to a defect in non-hematopoietic cells, as assessed using irradiated fetal liver chimeric mice
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• in a vWF-dependent deep vein thrombosis thrombo-inflammatory model, thrombus length and weight are reduced by ~60% although, macroscopically, thrombi show red and white parts similar to those in wild-type controls; 4 of 9 mice fail to develop a thrombus, whereas all wild-type controls develop thrombi
• in a vWF-dependent myocardial ischemia-reperfusion thrombo-inflammatory model, platelet deposition and aggregate size in the microcirculation are reduced by ~50% relative to wild-type controls
• however, no differences in time to complete vessel occlusion are observed in platelet-driven arterial thrombosis models (mechanical-induced injury of the abdominal aorta and FeCl3-induced injury of mesenteric arterioles)
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cardiovascular system
N |
• mice show no structural alterations in blood vessels of the kidney, pancreas and ear, indicating that vasculature is grossly normal
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