title: ATP-binding cassette transporter A1 expression is decreased in preeclamptic placentas.
abstract: Preeclampsia is a pregnancy-specific multisystem disorder characterized by hypertension and proteinuria. Accentuated maternal hyperlipidemia, especially high serum levels of oxidized low-density lipoprotein (oxLDL), is one of the features of preeclampsia. We previously reported that lectin-like oxidized LDL receptor 1 (LOX-1) expression was decreased in preeclamptic placentas. Here, we show that decreased LOX-1 expression is associated with low expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) in the placenta. The ABCA1 mediates cellular efflux of cholesterol, and liver X receptors (LXRs) are its predominant transcriptional regulators. Both ABCA1 and LXR expressions were significantly lower in preeclamptic placentas than those in normal controls. Oxidized LDL upregulated ABCA1 expression, while LOX-1 blockade resulted in the alleviation of increasing ABCA1 messenger RNA in JAR cells. These results suggest that low LOX-1 expression may lead to insufficient oxLDL uptake, thereby contributing to reduced LXR activation and decreased ABCA1 expression in preeclamptic placentas.
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Chigusa
authors.forename: Eiji
authors.initials: E
authors.lastname: Kondoh
authors.forename: Haruta
authors.initials: H
authors.lastname: Mogami
authors.forename: Fumitomo
authors.initials: F
authors.lastname: Nishimura
authors.forename: Mari
authors.initials: M
authors.lastname: Ujita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Fujita
authors.forename: Keiji
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C495137:OLR1 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein