Abstract
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.
Highlights
Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life
The cause of preeclampsia remains unknown; different lines of evidence indicate that abnormal lipid metabolism is involved in the pathogenesis; the acute atherosis seen in uteroplacental beds in preeclamptic women is one of these [5]
Cholesterol efflux Cholesterol efflux capacity of both maternal and fetal plasma was increased in preeclampsia; cholesterol efflux capacity was lower in fetal compared with maternal plasma in both study groups (31% and 24%, respectively; P < 0.001 for both; Fig. 1A)
Summary
Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. 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). HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). 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.—Mistry, H. Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia. Preeclampsia is one of the three leading causes of maternal morbidity and mortality worldwide, complicating around 2–8% of pregnancies [1] This disorder increases the chance of adverse perinatal outcomes, such as fetal growth restriction and preterm delivery [2].
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