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Review
. 2023 Apr 22;11(5):1237.
doi: 10.3390/biomedicines11051237.

Tissue Factor Pathway Inhibitors as Potential Targets for Understanding the Pathophysiology of Preeclampsia

Hiroshi Kobayashi  1   2 , Sho Matsubara  2   3 , Chiharu Yoshimoto  2   4 , Hiroshi Shigetomi  2   5 , Shogo Imanaka  1   2
Affiliations
Review

Tissue Factor Pathway Inhibitors as Potential Targets for Understanding the Pathophysiology of Preeclampsia

Hiroshi Kobayashi et al. Biomedicines. .

Abstract

Background: 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.

Methods: A literature search was performed from inception to 30 June 2022 in the PubMed and Google Scholar databases.

Results: 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.

Conclusions: 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.

Keywords: coagulation; fibrinolysis; preeclampsia; tissue factor; tissue factor pathway inhibitor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The number of articles identified by searching for keyword combinations.
Figure 2
Figure 2
Conserved motif arrangement in proteins of the TFPI family.
Figure 3
Figure 3
Concentrations of TF, TFPI1, and TFPI2 in maternal blood and placental tissue from healthy pregnant women and preeclamptic patients. The thicker the arrow in the figure, the greater the production volume.
See this image and copyright information in PMC

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