Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia
Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia
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DOI：
10.1194/jlr.m071985
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发表时间：
2017-06-01
影响因子：
6.5
通讯作者：
Escher, GeneviSve
中科院分区：
文献类型：
--
作者：
Mistry, Hiten D.;Kurlak, Lesia O.;Escher, GeneviSve
先兆子痫是一种妊娠特异性疾病，导致晚年心血管风险增加。胆固醇流出能力的降低与CVD有关。我们假设，在先兆子痫中，母体/胎儿血浆胆固醇外排中断，胎盘固醇27-羟化酶（CYP 27 A1）和载脂蛋白A1结合蛋白（AIBP）的浓度也存在差异。总胆固醇、高密度脂蛋白和ABCA 1介导的胆固醇流出用先兆子痫妇女和血压正常对照组的母体和胎儿血浆进行（均为n = 17）。apoA 1和apoE通过化学发光定量，27-羟基胆固醇（27-OHC）通过GC-MS定量。免疫组织化学法用于测定CYP 27 A1、AIBP、apoA 1、apoE和SRB 1的胎盘表达/定位。先兆子痫患者母体和胎儿总胆固醇和HDL介导的胆固醇外排能力增加（10-20%），但ABCA 1介导的外排能力降低（20-35%; P < 0.05）。子痫前期孕妇和胎儿apoE浓度较高。先兆子痫组胎儿血浆27-OHC水平明显低于正常对照组（P < 0.05）。胎盘组织中CYP 27 A1和AIBP蛋白的表达均位于胎儿血管周围，且在子痫前期患者中表达显著增加（P = 0.04）。妊高征患者胎盘27-OHC浓度明显升高（P < 0.05）。HDL介导的胆固醇外排能力和胎盘CYP 27 A1/27-OHC增加可能是先兆子痫的一种补救机制，可从细胞中清除胆固醇，限制脂质过氧化，增加胎盘血管生成。
Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples (P < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia (P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia (P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis.