Protein Z, an anticoagulant protein with expanding role in reproductive biology

Abstract

Protein Z (PZ) is a vitamin K-dependent factor characterized by its homology to other vitamin K-dependent factors (factors VII, IX, and X, protein C and protein S), but lacks any enzymatic activity. Instead, PZ acts as a cofactor for the inhibition of factor Xa through the serpin PZ-dependent protease inhibitor (ZPI). PZ deficiency is associated with a procoagulant state, highlighted by excessive FXa secretion and thrombin production, and is linked with several thrombotic disorders, including arterial vascular and venous thromboembolic diseases. A role for the PZ-ZPI complex in the regulation of physiological pregnancy has been demonstrated, highlighted by the progressive elevation in PZ levels in the first trimester of gestation, which then steadily decline toward delivery. An association between altered plasma PZ concentrations and adverse pregnancy outcomes (recurrent miscarriage, stillbirth, preeclampsia, intrauterine growth restriction, and placental abruption) has been reported. The mechanism by which PZ deficiency leads to adverse pregnancy outcomes is not clear, but it is multifactorial. It may be attributed to the anti-PZ IgG and IgM autoantibodies, which apparently act independently of classical antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-b2-glycoprotein I antibodies). PZ deficiency has also been reported to be constitutional, and a number of variants in the PROZ (PZ) gene and SERPINA10 (ZPI) gene are linked with specific adverse pregnancy complications. This review summarizes the relationship between adverse pregnancy outcomes and acquired and constitutional PZ-ZPI deficiency, in order to understand whether or not PZ deficiency could be considered as a risk factor for poor pregnancy outcomes.

Multi-Tissue Omics Analyses Reveal Molecular Regulatory Networks for Puberty in Composite Beef Cattle

“…The largest DE was observed for the genes of ribosomal protein L39 gene ( RPL39 ) essential for cell growth development and Vitamin K-dependent protein Z ( PROZ ) known to be involved in the venous thrombosis and pregnancy in several human populations [31], [32]. The RPL39 gene was initially associated with reduced body size and diminished fertility [32], [33] and more recently with testicular function [34]. This gene was also DE in hypothalamus and longissimus dorsi muscle (up-regulated at puberty).…”

Serum amyloid A, protein Z, and C4b-binding protein β chain as new potential biomarkers for pulmonary tuberculosis

“…It exists in the form of a PROZ/ZPI complex with PROZ-dependent protease inhibitor (ZPI), and the PROZ/ZPI complex can inhibit the activation of factor X a in the presence of SERPINA10, Ca 2+ , and phospholipids [34,35], and prevent thrombin generation in the early stage of coagulation [36,37]. High levels of PROZ have been found in patients with ischemic stroke [21,22].…”

Update of the human and mouse SERPINgene superfamily

“…Mutations in the SERPINA1 gene have been linked with early-onset pulmonary emphysema, neonatal hepatitis, liver cirrhosis, and sometimes panniculitis and vasculitis [74,75]. SERPINA5 mutations have been linked with increased papillary thyroid cancer risk [76], and mutations in SERPINA10 have been linked to pregnancy complications [77]. Predisposition to familial venous thromboembolic disease has been linked to mutations in SERPINC1 [78,79].…”