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.

Apolipoprotein A1 mimetic peptide ATI-5261 reverses arterial stiffness at late pregnancy and early postpartum in a COMT−/− mouse model of preeclampsia

“…Consistent with previous studies in humans [ 19 , 20 , 22 ], placental ABCA1 expressions were decreased in the COMT −/− mice model of PE. The ABC transporters comprise a family of functionally diverse polytopic transmembrane proteins and are able to translocate a wide variety of substrates, including amino acids, lipids, ions, peptides and drugs, across extracellular and intracellular biological membranes [ 68 ].…”

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance

“…In a subsequent study, the same group also showed that the decreased LOX-1 expression could lead to insufficient uptake of Ox-LDL and subsequently leading to decreased LXR activation and thereby decreasing ABCA1 expression. These findings indicate that ABCA1 expression is decreased in preclamptic placentae and also provides new insights in understanding pathophysiology of preeclampsia (35). However, these results are different with those reported by Plosch et al, indicating an upregulation of ABCA1 in early onset preeclamptic placentae but not significant elevation in late onset preeclampsia (32).…”

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

“…In addition, preeclampsia affects the long-term outcome of both mothers and their offspring ( Bokslag et al, 2016 ). Serum levels of triglycerides, LDLs, small dense LDLs that are susceptible to oxidation, as well as oxLDLs are higher in women with preeclampsia compared to healthy pregnant women ( Chigusa et al, 2013 ). Murata et al (1996) found decreased expression of VLDLR and LDLR mRNA in third trimester placentas derived from preeclamptic women.…”

“…Thus, the LXR-mediated upregulation of ABC-transporters in GDM appeared to restore cholesterol homeostasis ( Sun et al, 2018 ). Alterations of expression levels of ABCA1 and ABCG1 in total placental tissue in case of pregnancy diseases such as GDM, preeclampsia, hypoxia, or antiphospholipid-syndrome were reported, but the results are partly inconsistent ( Albrecht et al, 2007 ; Plosch et al, 2007 , 2010 ; Korner et al, 2012 ; Baumann et al, 2013 ; Chigusa et al, 2013 ; Dube et al, 2013 ; Liu et al, 2014 ; Huang et al, 2018 ).…”