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a Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Key Words: decidua • tissue factor • hemostasis • angiogenesis • preeclampsia
Address for correspondence: Frederick Schatz, Ph.D., Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, Room 335 FMB, P.O. Box 208063, New Haven, CT, 06510. Voice: +1-203-737-5238; fax: +1-203-737-2327. frederick.schatz{at}yale.edu
During extravascular trophoblast (EVT) invasion of the decidua, thrombin generated from decidual cell–expressed tissue factor (TF) forms a "hemostatic envelope" that protects against hemorrhage during the initial breaching of capillaries by EVTs and subsequent invasion and remodeling of the spiral arteries and arterioles. Preeclampsia, the world's leading cause of fetal and maternal morbidity and mortality, stems from shallow trophoblast invasion leading to incomplete vascular remodeling that impairs uteroplacental blood flow. A considerable subset of cases of preeclampsia is associated with decidual hemorrhage and maternal thrombophilias, which form excess thrombin from decidual cell–expressed TF. Thrombin affects several cell functions by binding to protease-activated receptors. In first-trimester decidual cells, thrombin enhances expression of sFlt-1, which can block the angiogenic effects of vascular endothelial growth factor (VEGF) and placental growth factor. By contrast, thrombin does not affect decidual cell VEGF expression. Thrombin-enhanced sFlt-1 expression by decidual cells, the predominant cell type encountered by invading cytotrophoblasts, could promote preeclampsia by interfering with angiogenesis-dependent vascular remodeling to reduce uteroplacental blood flow.
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