Kobayashi Hiroshi, Matsubara Sho, Yoshimoto Chiharu, Shigetomi Hiroshi, Imanaka Shogo
Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan.
Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
Biomedicines. 2023 Apr 22;11(5):1237. doi: 10.3390/biomedicines11051237.
Preeclampsia is a hypertensive disorder of pregnancy that causes maternal and perinatal morbidity and mortality worldwide. Preeclampsia is associated with complex abnormalities of the coagulation and fibrinolytic system. Tissue factor (TF) is involved in the hemostatic system during pregnancy, while the Tissue Factor Pathway Inhibitor (TFPI) is a major physiological inhibitor of the TF-initiated coagulation cascade. The imbalance in hemostatic mechanisms may lead to a hypercoagulable state, but prior research has not comprehensively investigated the roles of TFPI1 and TFPI2 in preeclamptic patients. In this review, we summarize our current understanding of the biological functions of TFPI1 and TFPI2 and discuss future directions in preeclampsia research.
A literature search was performed from inception to 30 June 2022 in the PubMed and Google Scholar databases.
TFPI1 and TFPI2 are homologues with different protease inhibitory activities in the coagulation and fibrinolysis system. TFPI1 is an essential physiological inhibitor of the TF-initiated extrinsic pathway of coagulation. On the other hand, TFPI2 inhibits plasmin-mediated fibrinolysis and exerts antifibrinolytic activity. It also inhibits plasmin-mediated inactivation of clotting factors and maintains a hypercoagulable state. Furthermore, in contrast to TFPI1, TFPI2 suppresses trophoblast cell proliferation and invasion and promotes cell apoptosis. TFPI1 and TFPI2 may play important roles in regulating the coagulation and fibrinolytic system and trophoblast invasion to establish and maintain successful pregnancies. Concentrations of TF, TFPI1, and TFPI2 in maternal blood and placental tissue are significantly altered in preeclamptic women compared to normal pregnancies.
TFPI protein family may affect both the anticoagulant (i.e., TFPI1) and antifibrinolytic/procoagulant (i.e., TFPI2) systems. TFPI1 and TFPI2 may function as new predictive biomarkers for preeclampsia and navigate precision therapy.
子痫前期是一种妊娠期高血压疾病，在全球范围内导致孕产妇和围产儿发病和死亡。子痫前期与凝血和纤溶系统的复杂异常有关。组织因子（TF）在妊娠期间参与止血系统，而组织因子途径抑制剂（TFPI）是TF启动的凝血级联反应的主要生理抑制剂。止血机制的失衡可能导致高凝状态，但先前的研究尚未全面研究TFPI1和TFPI2在子痫前期患者中的作用。在本综述中，我们总结了目前对TFPI1和TFPI2生物学功能的理解，并讨论了子痫前期研究的未来方向。
在PubMed和谷歌学术数据库中进行了从起始到2022年6月30日的文献检索。
TFPI1和TFPI2是在凝血和纤溶系统中具有不同蛋白酶抑制活性的同源物。TFPI1是TF启动的外源性凝血途径的重要生理抑制剂。另一方面，TFPI2抑制纤溶酶介导的纤维蛋白溶解并发挥抗纤溶活性。它还抑制纤溶酶介导的凝血因子失活并维持高凝状态。此外，与TFPI1不同，TFPI2抑制滋养层细胞增殖和侵袭并促进细胞凋亡。TFPI1和TFPI2可能在调节凝血和纤溶系统以及滋养层侵袭以建立和维持成功妊娠中发挥重要作用。与正常妊娠相比，子痫前期妇女母体血液和胎盘组织中TF、TFPI1和TFPI2的浓度发生了显著变化。
TFPI蛋白家族可能影响抗凝（即TFPI1）和抗纤溶/促凝（即TFPI2）系统。TFPI1和TFPI2可能作为子痫前期的新预测生物标志物并指导精准治疗。
