| First Author | Smith LH | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 1 | Pages | 132-4 |
| PubMed ID | 16160004 | Mgi Jnum | J:126198 |
| Mgi Id | MGI:3760701 | Doi | 10.1182/blood-2005-07-2681 |
| Citation | Smith LH, et al. (2006) Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis. Blood 107(1):132-4 |
| abstractText | Hepatic veno-occlusive disease (VOD) is a common complication of high-dose chemotherapy associated with bone marrow transplantation. While the pathogenesis of VOD is uncertain, plasminogen activator inhibitor-1 (PAI-1) has emerged as a diagnostic marker and predictor of VOD in humans. In this study, we investigated the role of PAI-1 in a murine model of VOD produced by long-term nitric oxide synthase inhibition using L-NAME. After 6 weeks, wild-type (WT) mice developed extensive fibrinoid hepatic venous thrombi and biochemical evidence of hepatic injury and dysfunction. In contrast, PAI-1-deficient mice were largely protected from the development of hepatic vein thrombosis. Furthermore, WT mice that received tiplaxtinin, an antagonist of PAI-1, were effectively protected from L-NAME-induced thrombosis. Taken together, these data indicate that NO and PAI-1 play pivotal and antagonistic roles in hepatic vein thrombosis and that PAI-1 is a potential target in the prevention and treatment of VOD in humans. |
