OBJECTIVES: The Liver X receptors (LXR) alpha and beta and their target genes such as the ATP-binding cassette (ABC) transporters have been shown to be crucially involved in the regulation of cellular cholesterol homeostasis. The aim of this study was to characterize the role of LXR alpha/beta in the human placenta under normal physiological circumstances and in preeclampsia. STUDY DESIGN: We investigated the expression pattern of the LXRs and their target genes in the human placenta during normal pregnancy and in preeclampsia. Placental explants and cell lines were studied under different oxygen levels and pharmacological LXR agonists. MAIN OUTCOME MEASURES: Gene expressions (Taqman PCR) and protein levels (Western Blot) were combined with immunohistochemistry to analyze the expression of LXR and its target genes. RESULTS: In the human placenta, LXRA and LXRB expression increased during normal pregnancy. This was paralleled by the expression of their prototypical target genes, e.g., the cholesterol transporter ABCA1. Interestingly, early-onset preeclamptic placentae revealed a significant upregulation of ABCA1. Culture of JAr trophoblast cells and human first trimester placental explants under low oxygen lead to increased expression of LXRA and ABCA1 which was further enhanced by the LXR agonist T0901317. CONCLUSIONS: LXRA together with ABCA1 are specifically expressed in the human placenta and can be regulated by hypoxia. Deregulation of this system in early preeclampsia might be the result of placental hypoxia and hence might have consequences for maternal-fetal cholesterol transport.
OBJECTIVES: The Liver X receptors (LXR) alpha and beta and their target genes such as the ATP-binding cassette (ABC) transporters have been shown to be crucially involved in the regulation of cellular cholesterol homeostasis. The aim of this study was to characterize the role of LXR alpha/beta in the human placenta under normal physiological circumstances and in preeclampsia. STUDY DESIGN: We investigated the expression pattern of the LXRs and their target genes in the human placenta during normal pregnancy and in preeclampsia. Placental explants and cell lines were studied under different oxygen levels and pharmacological LXR agonists. MAIN OUTCOME MEASURES: Gene expressions (Taqman PCR) and protein levels (Western Blot) were combined with immunohistochemistry to analyze the expression of LXR and its target genes. RESULTS: In the human placenta, LXRA and LXRB expression increased during normal pregnancy. This was paralleled by the expression of their prototypical target genes, e.g., the cholesterol transporter ABCA1. Interestingly, early-onset preeclamptic placentae revealed a significant upregulation of ABCA1. Culture of JAr trophoblast cells and human first trimester placental explants under low oxygen lead to increased expression of LXRA and ABCA1 which was further enhanced by the LXR agonist T0901317. CONCLUSIONS: LXRA together with ABCA1 are specifically expressed in the human placenta and can be regulated by hypoxia. Deregulation of this system in early preeclampsia might be the result of placental hypoxia and hence might have consequences for maternal-fetal cholesterol transport.
Authors: Sigrid Vondra; Victoria Kunihs; Tanja Eberhart; Karin Eigner; Raimund Bauer; Peter Haslinger; Sandra Haider; Karin Windsperger; Günter Klambauer; Birgit Schütz; Mario Mikula; Xiaowei Zhu; Alexander E Urban; Roberta L Hannibal; Julie Baker; Martin Knöfler; Herbert Stangl; Jürgen Pollheimer; Clemens Röhrl Journal: J Lipid Res Date: 2019-09-17 Impact factor: 5.922
Authors: Anand A Joshi; Soniya S Vaidya; Marie V St-Pierre; Andrei M Mikheev; Kelly E Desino; Abner N Nyandege; Kenneth L Audus; Jashvant D Unadkat; Phillip M Gerk Journal: Pharm Res Date: 2016-09-19 Impact factor: 4.200
Authors: Laura E Coats; Daniel R Bamrick-Fernandez; Allison M Ariatti; Bhavisha A Bakrania; Adam Z Rawls; Norma B Ojeda; Barbara T Alexander Journal: Am J Physiol Regul Integr Comp Physiol Date: 2020-11-11 Impact factor: 3.619