Vessel wall BAMBI contributes to hemostasis and thrombus stability.

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Title: Vessel wall BAMBI contributes to hemostasis and thrombus stability.
Authors: Salles-Crawley, II
Monkman, JH
Ahnstroem, J
Lane, DA
Crawley, JTB
Item Type: Journal Article
Abstract: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is a transmembrane protein related to the transforming growth factor-β superfamily, and is highly expressed in platelets and endothelial cells. We previously demonstrated its positive role in thrombus formation using a zebrafish thrombosis model. In the present study, we used Bambi-deficient mice and radiation chimeras to evaluate the function of this receptor in the regulation of both hemostasis and thrombosis. We show that Bambi−/− and Bambi+/− mice exhibit mildly prolonged bleeding times compared with Bambi+/+ littermates. In addition, using 2 in vivo thrombosis models in mesenterium or cremaster muscle arterioles, we demonstrate that Bambi-deficient mice form unstable thrombi compared with Bambi+/+ mice. No defects in thrombin generation in Bambi−/− mouse plasma could be detected ex vivo. Moreover, the absence of BAMBI had no effect on platelet counts, platelet activation, aggregation, or platelet procoagulant function. Similar to Bambi−/− mice, Bambi−/− transplanted with Bambi+/+ bone marrow formed unstable thrombi in the laser-induced thrombosis model that receded more rapidly than thrombi that formed in Bambi+/+ mice receiving Bambi−/− bone marrow transplants. Taken together, these results provide strong evidence for an important role of endothelium rather than platelet BAMBI as a positive regulator of both thrombus formation and stability.
Issue Date: 1-May-2014
Date of Acceptance: 7-Mar-2014
URI: http://hdl.handle.net/10044/1/61073
DOI: https://dx.doi.org/10.1182/blood-2013-10-534024
ISSN: 0006-4971
Publisher: American Society of Hematology
Start Page: 2873
End Page: 2881
Journal / Book Title: Blood
Volume: 123
Issue: 18
Copyright Statement: © 2014 by The American Society of Hematology
Sponsor/Funder: British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Funder's Grant Number: FS/10/004/28165
FS/12/60/29874
FS/12/60/29874
FS/10/004/28165
Keywords: Science & Technology
Life Sciences & Biomedicine
Hematology
TRANSFORMING-GROWTH-FACTOR
MEMBRANE-BOUND INHIBITOR
BONE MORPHOGENETIC PROTEIN
FORMATION IN-VIVO
TGF-BETA
HUMAN-PLATELETS
COLORECTAL-CANCER
TRANSCRIPTIONAL REGULATION
PSEUDORECEPTOR BAMBI
PRESSURE-OVERLOAD
Animals
Bleeding Time
Blood Coagulation
Blood Platelets
Disease Models, Animal
Endothelium, Vascular
Female
Genotype
Hemostasis
Male
Membrane Proteins
Mice
Mice, Knockout
Thrombosis
HEMATOLOGY
1102 Cardiovascular Medicine And Haematology
1103 Clinical Sciences
1114 Paediatrics And Reproductive Medicine
Immunology
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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