Expression of thrombin receptors in endothelial cells and neutrophils from normal and preeclamptic pregnancies
Expression of thrombin receptors in endothelial cells and neutrophils from normal and preeclamptic pregnancies
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DOI：
10.1210/jc.87.8.3728
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发表时间：
2002-08-01
影响因子：
5.8
通讯作者：
Lucas, MJ
中科院分区：
文献类型：
--
作者：
Wang, YP;Gu, Y;Lucas, MJ
凝血酶受体，即蛋白酶激活受体（PAR），在内皮细胞（EC）和中性粒细胞中表达，并直接影响血小板功能和血栓形成。虽然内皮功能障碍和中性粒细胞活化已被证明在先兆子痫（PE）的妇女，PAR的表达和调节还没有被定义在PE。在这项研究中，我们测量了PAR在正常和先兆子痫妊娠的内皮细胞和中性粒细胞中的表达。我们还研究了胎盘因素对这些细胞中PAR表达的影响。从正常和先兆子痫妊娠的脐带（人脐静脉EC）分离EC。从非妊娠、无并发症妊娠和先兆子痫妇女的血液中分离中性粒细胞。从第一代（P1）EC（正常和PE）和与来自正常和先兆子痫胎盘培养物的条件培养基孵育的正常P1 EC中提取总RNA。用核糖核酸酶保护法检测凝血酶受体（PAR 1）、PAR 2和PAR 3的mRNA表达。将甘油醛3-磷酸脱氢酶的表达用作每个样品的内部对照。我们发现：1）与正常妊娠的内皮细胞相比，PE的内皮细胞中PAR 1的表达增强; 2）PAR 2在PE的内皮细胞中表达，而在正常的内皮细胞中不表达; 3）来自非妊娠妇女、正常和先兆子痫妊娠的中性粒细胞表达PAR 2，而仅来自正常和先兆子痫妊娠的中性粒细胞表达PAR 1;子痫前期胎盘释放因子上调内皮细胞PARI和PAR 2的表达，但对中性粒细胞无影响。我们的结论是PAR 1和PAR 2的mRNA表达增加来自先兆子痫妊娠的EC。中性粒细胞凝血酶受体表达的上调可能是妊娠期间的一种独特现象，但并非PE所独有。胎盘释放的因子可能是调节内皮细胞PAR表达的候选者，并可能参与PE中血小板活化和血管内皮功能障碍。
Thrombin receptors, i.e. proteinase-activated receptors (PARs), are expressed in endothelial cells (ECs) and neutrophils and directly affect platelet function and thrombosis. Although endothelial dysfunction and neutrophil activation have been demonstrated in women with preeclampsia (PE), the expression and regulation of PARs have not been defined in PE. In this study, we measured the expression of PARs in ECs and in neutrophils derived from normal and preeclamptic pregnancies. We also examined the effects of placental factors on PAR expression in these cells in vitro. ECs were isolated from umbilical cords (human umbilical vein ECs) from normal and preeclamptic pregnancies. Neutrophils were isolated from blood obtained from nonpregnant, uncomplicated pregnant, and preeclamptic women. Total RNA was extracted from the first-passage (P1) ECs (normal and PE) and from normal P1 ECs incubated with conditioned media derived from normal and preeclamptic placental cultures. The mRNA expression of thrombin receptor (PAR1), PAR2, and PAR3 was measured by ribonuclease protective assay. The expression of glyceraldehyde 3-phosphate dehydrogenase was used as an internal control for each sample. We found that: 1) PAR1 expression was enhanced in ECs from PE, compared with ECs from normal pregnancies; 2) PAR2 expression was expressed in PE ECs but not in normal ECs; 3) neutrophils from nonpregnant women, normal, and preeclamptic pregnancies expressed PAR2, whereas only neutrophils from normal and preeclamptic pregnancies expressed PAR1; and 4) factors released from preeclamptic placenta up-regulated PARI and PAR2 expression in ECs but not in neutrophils. We conclude that mRNA expression of PAR1 and PAR2 is increased in ECs derived from preeclamptic pregnancies. Up-regulation of thrombin receptor expression in neutrophils may be a unique phenomenon during pregnancy but not apparently unique to PE. Factors released from the placenta are likely candidates in regulating PAR expression in ECs and may contribute to the platelet activation and vascular endothelial dysfunction in PE.