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

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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 pheno-type 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.

Original languageEnglish
Pages (from-to)4973-4978
Number of pages6
JournalBlood
Volume111
Issue number10
DOIs
StatePublished - May 15 2008

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