Protein Z–dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency
Open Access
- 15 May 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 111 (10), 4973-4978
- https://doi.org/10.1182/blood-2007-12-126391
Abstract
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 VLeiden 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.This publication has 39 references indexed in Scilit:
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