| First Author | Crawley JTB | Year | 2019 |
| Journal | J Thromb Haemost | Volume | 17 |
| Issue | 11 | Pages | 1935-1949 |
| PubMed ID | 31351019 | Mgi Jnum | J:294292 |
| Mgi Id | MGI:6455258 | Doi | 10.1111/jth.14593 |
| Citation | Crawley JTB, et al. (2019) Defective fibrin deposition and thrombus stability in Bambi(-/-) mice are mediated by elevated anticoagulant function. J Thromb Haemost 17(11):1935-1949 |
| abstractText | BACKGROUND: Bone morphogenetic and activin membrane-bound inhibitor (BAMBI) is a transmembrane protein related to the type I transforming growth factor- beta (TGF-beta) receptor family that is present on both platelets and endothelial cells (ECs). Bambi-deficient mice exhibit reduced hemostatic function and thrombus stability characterized by an increased embolization. OBJECTIVE: We aimed to delineate how BAMBI influences endothelial function and thrombus stability. METHODS: Bambi-deficient mice were subjected to the laser-induced thrombosis model where platelet and fibrin accumulation was evaluated. Expression of thrombomodulin and tissue factor pathway inhibitor (TFPI) was also assessed in these mice. RESULTS: Thrombus 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 ECs 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. Endothelial cells 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. CONCLUSIONS: We demonstrate that endothelial BAMBI influences fibrin generation and thrombus stability by modulating thrombomodulin and TFPI anticoagulant function of the endothelium; we also highlight the importance of these anticoagulant proteins in the laser-induced thrombosis model. |
