Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis.

Smith LH, Dixon JD, Stringham JR, Eren M, Elokdah H, Crandall DL, Washington K, Vaughan DE
Blood. 2006 107 (1): 132-4

PMID: 16160004 · PMCID: PMC1895352 · DOI:10.1182/blood-2005-07-2681

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.

MeSH Terms (12)

Animals Budd-Chiari Syndrome Disease Models, Animal Hepatic Veno-Occlusive Disease Indoleacetic Acids Indoles Mice Mice, Knockout NG-Nitroarginine Methyl Ester Nitric Oxide Nitric Oxide Synthase Plasminogen Activator Inhibitor 1

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