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@article{Crawley:2019:10.1111/jth.14593,
author = {Crawley, JTB and Zalli, A and Monkman, JH and Petri, A and Lane, DA and Ahnstrm, J and SallesCrawley, II},
doi = {10.1111/jth.14593},
journal = {Journal of Thrombosis and Haemostasis},
title = {Defective fibrin deposition and thrombus stability in Bambi/ mice is mediated by elevated anticoagulant function},
url = {http://dx.doi.org/10.1111/jth.14593},
year = {2019}
}

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TY  - JOUR
AB  - BackgroundBAMBI is a transmembrane protein related to the type I TGFβ receptor family that is present on both platelets and endothelial cells (EC). Bambideficient mice exhibit reduced hemostatic function and thrombus stability characterized by an increased embolization.ObjectiveWe aimed to delineate how BAMBI influences endothelial function and thrombus stability.MethodsBambideficient mice were subjected to the laserinduced thrombosis model where platelet and fibrin accumulation was evaluated. Expression of thrombomodulin and TFPI was also assessed in these mice.ResultsThrombus instability in Bambi/ mice was associated with a profound defect in fibrin deposition. Injection of hirudin into Bambi+/+ mice prior to thrombus formation recapitulated the Bambi/ thrombus instability phenotype. In contrast, hirudin had no additional effect upon thrombus formation in Bambi/ mice. Deletion of Bambi in EC resulted in mice with defective thrombus stability caused by decreased fibrin accumulation. Increased levels of the anticoagulant proteins TFPI and thrombomodulin, were detected in Bambi/ mouse lung homogenates. EC isolated from Bambi/ mouse lungs exhibited enhanced ability to activate protein C due to elevated thrombomodulin levels. Blocking thrombomodulin and TFPI in vivo fully restored fibrin accumulation and thrombus stability in Bambi/ mice.ConclusionsWe demonstrate that endothelial BAMBI influences fibrin generation and thrombus stability by modulating thrombomodulin and TFPI anticoagulant function of the endothelium, and also highlight the importance of these anticoagulant proteins in the laserinduced thrombosis model.
AU  - Crawley,JTB
AU  - Zalli,A
AU  - Monkman,JH
AU  - Petri,A
AU  - Lane,DA
AU  - Ahnstrm,J
AU  - SallesCrawley,II
DO  - 10.1111/jth.14593
PY  - 2019///
SN  - 1538-7933
TI  - Defective fibrin deposition and thrombus stability in Bambi/ mice is mediated by elevated anticoagulant function
T2  - Journal of Thrombosis and Haemostasis
UR  - http://dx.doi.org/10.1111/jth.14593
UR  - http://hdl.handle.net/10044/1/72208
ER  -

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