Coagulation and fibrinolysis related cytokine imbalance in preeclampsia: the role of placental trophoblasts

Objective: Cytokine imbalance might have a pivotal role in hypercoagulability seen in preeclampsia. Our objective was to determine the relationship of blood coagulation related factors in placental tissue and peripheral blood in preeclamptic and normal pregnancies. Methods: We compared mRNA and protein levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and tissue factor (TF) in the placenta of normal and preeclamptic pregnancies. Placental and peripheral blood t-PA and PAI-1 levels were examined. Trophoblasts were used to study the effects of hypoxia, hypoxia-reperfusion, and inflammatory cytokines on t-PA, PAI-1, tissue factor pathway inhibitor (TFPI), and TF. Results: PAI-1 and TF mRNA and protein levels were higher in placental tissue of preeclamptic pregnancies and in the peripheral blood of patients with preeclampsia. mRNA and protein secretion of TF, TFPI, PAI-1, but not t-PA, was increased in trophoblast cell culture under hypoxia and hypoxia-reoxygenation. Cell cultures with high levels of tumor necrosis factor-alpha (TNF-alpha) exhibited increased expression and secretion of TF and PAI-1, decreased TFPI, and no significant change of t-PA. Conclusions: Imbalanced synthesis of t-PA, PAI-1, TFPI, and TF in trophoblasts may contribute to hypercoagulability in patients with preeclampsia.