| First Author | Passam FH | Year | 2022 |
| Journal | J Autoimmun | Volume | 126 |
| Pages | 102747 | PubMed ID | 34794103 |
| Mgi Jnum | J:330422 | Mgi Id | MGI:7378606 |
| Doi | 10.1016/j.jaut.2021.102747 | Citation | Passam FH, et al. (2022) Betaeta-2-glycoprotein I exerts antithrombotic function through its domain V in mice. J Autoimmun 126:102747 |
| abstractText | Little is known about the physiological role of beta-2-glycoprotein I (beta2GPI) despite it being the major auto-antigen in the antiphospholipid syndrome. A systematic study of the role of beta2GPI in thrombus formation in vivo has not been performed to date. Herein, we report that beta2GPI deficient (-/-) mice have enhanced thrombus formation compared to wild type (WT) mice in a laser-induced arteriole and venule model of thrombosis. Furthermore, neutrophil accumulation and elastase activity was enhanced in thrombi of beta2GPI -/- compared with WT mice. The antithrombotic function of beta2GPI is dependent on its fifth domain (domain V); intravenous administration of the beta2GPI domain deletion mutant lacking domain V (human recombinant domain I-IV) had no effect on platelet and fibrin thrombus size in beta2GPI -/- or WT mice. On the contrary, intravenous administration of human recombinant domain V significantly inhibited platelet and fibrin thrombus size in both beta2GPI -/- mice and WT mice. These findings reveal a major role for beta2GPI as a natural anticoagulant and implicate domain V of beta2GPI as a potential antithrombotic therapy. |
