ATP-binding cassette transporter A1 expression is decreased in preeclamptic placentas

Reprod Sci. 2013 Aug;20(8):891-8. doi: 10.1177/1933719112468956. Epub 2012 Dec 28.

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.

Keywords: ABCA1; LOX-1; LXR; oxidized LDL; preeclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism*
  • Adult
  • Case-Control Studies
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Humans
  • Lipoproteins, LDL / metabolism
  • Liver X Receptors
  • Orphan Nuclear Receptors / metabolism
  • Placenta / metabolism*
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Scavenger Receptors, Class E / metabolism

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Lipoproteins, LDL
  • Liver X Receptors
  • OLR1 protein, human
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein