title: Vessel wall BAMBI contributes to hemostasis and thrombus stability.
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.
authors.affiliation: Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom.
authors.forename: Isabelle I
authors.initials: II
authors.lastname: Salles-Crawley
authors.forename: James H
authors.initials: JH
authors.lastname: Monkman
authors.forename: Josefin
authors.initials: J
authors.lastname: Ahnström
authors.forename: David A
authors.initials: DA
authors.lastname: Lane
authors.forename: James T B
authors.initials: JT
authors.lastname: Crawley
mesh_terms: D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006487:Hemostasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013927:Thrombosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*
chemical_list: C485672:Bambi protein, mouse; D008565:Membrane Proteins