Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia

被引:43
作者
Mistry, Hiten D. [1 ,2 ]
Kurlak, Lesia O. [2 ]
Mansour, Yosef T. [3 ]
Zurkinden, Line [1 ]
Mohaupt, Markus G. [1 ]
Escher, GeneviSve [1 ]
机构
[1] Univ Bern, Dept Nephrol Hypertens Clin Pharmacol & Clin Res, Bern, Switzerland
[2] Univ Nottingham, Sch Med, Div Child Hlth Obstet & Gynecol, Nottingham, England
[3] Kings Coll London, Womens Hlth Acad Ctr, Div Womens Hlth, London, England
基金
瑞士国家科学基金会;
关键词
lipid/efflux; 27-hydroxycholesterol; apolipoproteins; pregnancy; hypertension; sterol; 27-hydroxylase; CARDIOVASCULAR-DISEASE; APOLIPOPROTEIN-E; STEROL; 27-HYDROXYLASE; WOMEN; PROTEIN; RISK; HDL; ACID; APOE;
D O I
10.1194/jlr.M071985
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1186 / 1195
页数:10
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