Mistry Hiten D, Kurlak Lesia O, Mansour Yosef T, Zurkinden Line, Mohaupt Markus G, Escher Geneviève
Department of Nephrology, Hypertension, Clinical Pharmacology, and Clinical Research, University of Bern, Bern, Switzerland
Division of Child Health, Obstetrics, and Gynecology, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
J Lipid Res. 2017 Jun;58(6):1186-1195. doi: 10.1194/jlr.M071985. Epub 2017 Apr 10.
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%; 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia ( = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( < 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.
子痫前期是一种妊娠特有的疾病，会导致日后心血管疾病风险增加。胆固醇流出能力降低与心血管疾病有关。我们假设，子痫前期患者母胎血浆中胆固醇流出会受到干扰，胎盘固醇27-羟化酶（CYP27A1）和载脂蛋白A1结合蛋白（AIBP）的浓度也会存在差异。采用子痫前期患者和血压正常的对照组（每组n = 17）的母胎血浆进行总胆固醇、高密度脂蛋白（HDL）及三磷酸腺苷结合盒转运体A1（ABCA1）介导的胆固醇流出实验。通过化学发光法定量检测载脂蛋白A1和载脂蛋白E，通过气相色谱-质谱联用仪检测27-羟胆固醇（又称27-OHC）。采用免疫组织化学法确定CYP27A1、AIBP、载脂蛋白A1、载脂蛋白E和清道夫受体B1（SRB1）在胎盘的表达及定位。子痫前期患者母胎总胆固醇及HDL介导的胆固醇流出能力增加（增加10%-20%），但ABCA1介导的流出能力降低（降低20%-35%；P<0.05）。子痫前期患者母胎载脂蛋白E浓度较高。子痫前期样本中胎儿血浆27-OHC水平降低（P<0.05）。CYP27A1和AIBP在胎盘的蛋白表达均定位于胎儿血管周围，且子痫前期显著增加（P = 0.04）。子痫前期胎盘27-OHC浓度也升高（P<0.05）。HDL介导的胆固醇流出能力增加及胎盘CYP27A1/27-OHC可能是子痫前期的一种挽救机制，可将胆固醇从细胞中清除，以限制脂质过氧化并增加胎盘血管生成。
