The Liver X Receptor (LXR) and its Target Gene ABCA1 are Regulated Upon Low Oxygen in Human Trophoblast Cells: A Reason for Alterations in Preeclampsia?

ATP-Binding Cassette Transporter A1 Expression Is Decreased in Preeclamptic Placentas

“…Intriguingly, our results were inconsistent with the previous studies. Plosch et al revealed the upregulation of ABCA1 in early-onset preeclamptic placentas, 15 and Albrecht et al reported the unchanged expression of ABCA1 in placentas from women with preeclampsia, while they found decreased Values were normalized to those of GAPDH. Data are presented as the mean + standard error of the mean.…”

Role of Nuclear Receptors Peroxisome Proliferator-Activated Receptors (PPARs) and Liver X Receptors (LXRs) in the Human Placental Pathophysiology

“…Apart from stimulating endoglin, LXR agonists may reduce trophoblast invasiveness by downregulating MMP9, as has been demonstrated in macrophages (Castrillo et al, 2003). The demonstration that LXR together with ABCA1 can be regulated by hypoxia is another argument of the LXR involvement in preeclampsia, where the oxygen tension is described as abnormal (Plösch et al, 2010).…”

“…Expression levels in preterm and term placentae are similar to each other, but significantly higher than in the first two trimesters of gestation. The obligate heterodimeric partner of the LXRs, RXR, was found to be constitutively expressed throughout gestation (Plösch et al, 2010). Furthermore, both LXRs have been demonstrated to be expressed in choriocarcinoma trophoblast cell lines, e.g., JAR and BeWo (Weedon-Fekjaer et al, 2005).…”

“…Role of Nuclear Receptors Peroxisome Proliferator-Activated Receptors (PPARs) and Liver X Receptors (LXRs) in the Human Placental Pathophysiology 389 may be increased in preeclampsia (Plösch et al, 2010). A positive correlation between placental LXR mRNA expression and placental free fatty acids was found in preeclampsia (Weedon-Fekjaer et al, 2010b).…”

Placental regulation of fetal nutrient supply

“…Treatment of mice with Smith-Lemli-Optiz syndrome (dysfunction on the de novo synthesis of cholesterol) using LXR agonists increases the placental ABCA1 carriers and the materno-fetal cholesterol transfer to the embryos increasing the placental cholesterol efflux [29]. Moreover, low oxygen, like in preeclampsia, increase LXR and ABCA1 carriers which may have consequences for maternal-fetal cholesterol transport [34].…”