title: Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.
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.
authors.affiliation: Department of Nephrology, Hypertension, Clinical Pharmacology, and Clinical Research, University of Bern, Bern, Switzerland hiten.mistry@nottingham.ac.uk.|Division of Child Health, Obstetrics, and Gynecology, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Hiten D
authors.initials: HD
authors.lastname: Mistry
authors.affiliation: Division of Child Health, Obstetrics, and Gynecology, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Lesia O
authors.initials: LO
authors.lastname: Kurlak
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London, London, United Kingdom.
authors.forename: Yosef T
authors.initials: YT
authors.lastname: Mansour
authors.affiliation: Department of Nephrology, Hypertension, Clinical Pharmacology, and Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Line
authors.initials: L
authors.lastname: Zurkinden
authors.affiliation: Department of Nephrology, Hypertension, Clinical Pharmacology, and Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Mohaupt
authors.affiliation: Department of Nephrology, Hypertension, Clinical Pharmacology, and Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Escher
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D005333:Fetus / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000097:blood; D009035:Mothers; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
chemical_list: C553277:AUNIP protein, human; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D008074:Lipoproteins; C076996:27-hydroxycholesterol; D002784:Cholesterol; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase
keywords: 27-hydroxycholesterol; apolipoproteins; hypertension; lipid/efflux; pregnancy; sterol 27-hydroxylase