Protein Z-dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency.

Jing Zhang, Yizheng Tu, Lan Lu, Nina Lasky, George J Broze

Blood 2008 May 15

filter terms:

Protein Z (PZ) is a plasma vitamin K-dependent protein that functions as a cofactor to dramatically enhance the inhibition of coagulation factor Xa by the serpin, protein Z-dependent protease inhibitor (ZPI). In vitro, ZPI not only inhibits factor Xa in a calcium ion-, phospholipid-, and PZ-dependent fashion, but also directly inhibits coagulation factor XIa. In murine gene-deletion models, PZ and ZPI deficiency enhances thrombosis following arterial injury and increases mortality from pulmonary thromboembolism following collagen/epinephrine infusion. On a factor V(Leiden) genetic background, ZPI deficiency produces a significantly more severe phenotype than PZ deficiency, implying that factor XIa inhibition by ZPI is physiologically relevant. The studies in mice suggest that human PZ and ZPI deficiency would be associated with a modest thrombotic risk with ZPI deficiency producing a more severe phenotype.

Citation

Jing Zhang, Yizheng Tu, Lan Lu, Nina Lasky, George J Broze. Protein Z-dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency. Blood. 2008 May 15;111(10):4973-8