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Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia
Hiten D Mistry1,2, Lesia O Kurlak2, Yosef T Mansour3
1Department of Nephrology, Hypertension, Clinical Pharmacology, and Clinical Research, University of Bern, Bern, Switzerland hiten.mistry@nottingham.ac.uk.
Insights
Preeclampsia alters cholesterol processing in maternal and fetal plasma, with decreased ABCA1 efflux but increased HDL efflux. Placental CYP27A1 and 27-OHC also increase, potentially as a protective response.
Area of Science:
- Cardiovascular Biology
- Reproductive Medicine
- Metabolic Disorders
Background:
- Preeclampsia is a pregnancy complication linked to future cardiovascular disease.
- Reduced cholesterol efflux capacity is associated with cardiovascular disease.
- Investigating cholesterol transport in preeclampsia may reveal mechanisms for cardiovascular risk.
Purpose of the Study:
- To investigate maternal and fetal plasma cholesterol efflux capacity in preeclampsia.
- To examine placental expression of sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP).
- To explore the role of cholesterol metabolism in preeclampsia pathophysiology and cardiovascular risk.
Main Methods:
- Measured total, HDL-, and ABCA1-mediated cholesterol effluxes using maternal and fetal plasma.
- Quantified apolipoproteins (apoA1, apoE) and 27-hydroxycholesterol (27-OHC).
- Assessed placental expression and localization of key proteins (CYP27A1, AIBP, apoA1, apoE, SRB1) via immunohistochemistry.
Main Results:
- Preeclampsia showed increased maternal/fetal total and HDL-mediated cholesterol efflux, but decreased ABCA1-mediated efflux.
- Elevated maternal/fetal apoE and placental CYP27A1, AIBP, and 27-OHC concentrations were observed in preeclampsia.
- Fetal plasma 27-OHC levels were decreased in preeclamptic samples.
Conclusions:
- Preeclampsia disrupts cholesterol efflux pathways, with altered ABCA1 and HDL mediation.
- Increased placental CYP27A1 and 27-OHC may represent a compensatory mechanism to manage cholesterol.
- These findings suggest potential pathways linking preeclampsia to later cardiovascular risk.
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.
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