Inhibiting trophoblast PAR-1 overexpression suppresses sFlt-1-induced anti-angiogenesis and abnormal vascular remodeling: a possible therapeutic approach for preeclampsia

作者：Yin Zhao, Yanfang Zheng, Xiaoxia Liu, Qingqing Luo, Di Wu, Xiaoping Liu, Li Zou · 发表于：Molecular Human Reproduction · 年份：2018 · DOI：10.1093/molehr/gax068 · 被引用次数：16 · 研究领域：Pregnancy and preeclampsia studies、Blood Coagulation and Thrombosis Mechanisms、Maternal and fetal healthcare

STUDY QUESTION: Is it possible to improve vascular remodeling by inhibiting the excessive expression of protease-activated receptor 1 (PAR-1) in trophoblast of abnormal placenta? SUMMARY ANSWER: Inhibition of trophoblast PAR-1 overexpression may promote placental angiogenesis and vascular remodeling, offering an alternative therapeutic approach for preeclampsia. WHAT IS KNOWN ALREADY: PAR-1 is high-affinity receptor of thrombin. Thrombin increases sFlt-1 secretion in trophoblast via the activation of PAR-1. It is reported that the expression of both thrombin and PAR-1 expression are increased in placentas of preeclampsia patients compared with normal placentas. STUDY DESIGN, SIZE, DURATION: Trophoblast cells were transfected with PAR-1 short hairpin RNA (shRNA) or PAR-1 overexpression plasmids in vitro. Tube formation assays and a villus-decidua co-culture system were used to study the effect of PAR-1 inhibition on placental angiogenesis and vascular remodeling, respectively. Placentas from rats with preeclampsia were transfected with PAR-1 shRNA to confirm the effect of inhibiting PAR-1 overexpression in placenta. PARTICIPANTS/MATERIALS, SETTING, METHODS: The trophoblast cell line HTR-8/SVneo was transfected with PAR-1 shRNA or PAR-1 overexpression plasmids. After 48 h, supernatant was collected and the level of sFlt-1 secretion was measured by ELISA. Human umbilical cord epithelial cells and a villus-decidua co-culture system were treated with conditioned media to study the...