| First Author | Shi H | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 34 | Pages | e2207592119 |
| PubMed ID | 35969769 | Mgi Jnum | J:340359 |
| Mgi Id | MGI:7437406 | Doi | 10.1073/pnas.2207592119 |
| Citation | Shi H, et al. (2022) Endothelial VWF is critical for the pathogenesis of vaso-occlusive episode in a mouse model of sickle cell disease. Proc Natl Acad Sci U S A 119(34):e2207592119 |
| abstractText | Vaso-occlusive episode (VOE) is a common and critical complication of sickle cell disease (SCD). Its pathogenesis is incompletely understood. von Willebrand factor (VWF), a multimeric plasma hemostatic protein synthesized and secreted by endothelial cells and platelets, is increased during a VOE. However, whether and how VWF contributes to the pathogenesis of VOE is not fully understood. In this study, we found increased VWF levels during tumor necrosis factor (TNF)-induced VOE in a humanized mouse model of SCD. Deletion of endothelial VWF decreased hemolysis, vascular occlusion, and organ damage caused by TNF-induced VOE in SCD mice. Moreover, administering ADAMTS13, the VWF-cleaving plasma protease, reduced plasma VWF levels, decreased inflammation and vaso-occlusion, and alleviated organ damage during VOE. These data suggest that promoting VWF cleavage via ADAMTS13 may be an effective treatment for reducing hemolysis, inflammation, and vaso-occlusion during VOE. |
