O10. Increased maternal and fetal HDL cholesterol efflux capacity and placental CYP27A1 expression in pre-eclampsia

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Introduction Pre-eclampsia is a pregnancy-specific condition affecting 2–7% of women, causing perinatal and maternal morbidity/mortality and predisposes both mother and fetus to increased risks of adult cardiovascular disease. A disturbance in the flow of cholesterol is linked to atherosclerosis and cardiovascular disease. Objective We measured cholesterol efflux capacity, apoA1, apoE and oxysterols, in maternal and fetal plasma and placental sterol 27-hydroxylase (CYP27A1) and apo-A1-binding-protein (AIBP) expression in normotensive control and pre-eclamptic pregnancies. Methods Cholesterol efflux assays were performed in RAW264.7 cells with maternal and matched fetal plasma of normotensive control or pre-eclamptic pregnancies (n = 17 in both). ApoA1, apoE were measured by ELISAs. Oxysterols were also measured by gas-chromatography–mass-spectrometry. Placental mRNA and protein expression/localisation of CYP27A1 and AIBP were measured in the same women by qPCR and immunohistochemistry. Results In pre-eclampsia, maternal and fetal cholesterol efflux capacity and fetal apoE were all increased ( P 0.05 for all), yet fetal cholesterol efflux capacity and apoE were lower in the small-for-gestational-age (SGA) subgroup (n = 6; P 0.05 for both). Fetal 27-hydroxycholesterol (27-OHC) concentrations were lower in babies born to pre-eclamptic mothers ( P 0.05 ) with no other observed differences in oxysterols. Fetal apparent CYP27A1 activities (calculated by ratios of 27-OHC/(27-OHC + total serum cholesterol) were also lower in the pre-eclampsia group ( P 0.05 ). Protein expression was localised around fetal vessels; CYP27A1 and AIBP proteins increased in pre-eclampsia (P = 0.04), but no differences were found in gene expression. Conclusions Increased maternal and fetal cholesterol efflux capacity in pre-eclampsia, which is a key step in reverse cholesterol transport, coupled with increased placental CYP27A1, could be a rescue mechanism to remove cholesterol from cells thus trying to reduce lipid peroxidation. However, increased placental AIBP suggests disturbed lipid homeostasis, which could disrupt placental angiogenesis, contributing to the endothelial dysfunction so characteristic of pre-eclampsia.