Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Direkt zur Navigaton springen.
Direkt zum Inhalt springen.

Navigation/Suche

"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Gerhard Pichler

Roland Malli

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Sun, Y; Kopp, S; Strutz, J; Gali, CC; Zandl-Lang, M; Fanaee-Danesh, E; Kirsch, A; Cvitic, S; Frank, S; Saffery, R; Björkhem, I; Desoye, G; Wadsack, C; Panzenboeck, U.
Gestational diabetes mellitus modulates cholesterol homeostasis in human fetoplacental endothelium.
Biochim Biophys Acta. 2018; 1863(9):968-979 Doi: 10.1016/j.bbalip.2018.05.005
Web of Science PubMed FullText FullText_MUG

Führende Autor*innen der Med Uni Graz: Panzenboeck Ute; Sun Yidan; Wadsack Christian
Co-Autor*innen der Med Uni Graz: Desoye Gernot; Fanaee-Danesh Elham; Frank Sasa; Gali Chaitanya Chakravarthi; Kirsch Andrijana; Kopp Susanne; Strutz Jasmin; Tokic Silvija; Zandl-Lang Martina
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: Gestational diabetes mellitus (GDM) is associated with excessive oxidative stress which may affect placental vascular function. Cholesterol homeostasis is crucial for maintaining fetoplacental endothelial function. We aimed to investigate whether and how GDM affects cholesterol metabolism in human fetoplacental endothelial cells (HPEC). HPEC were isolated from fetal term placental arterial vessels of GDM or control subjects. Cellular reactive oxygen species (ROS) were detected by H₂DCFDA fluorescent dye. Oxysterols were quantified by gas chromatography-mass spectrometry analysis. Genes and proteins involved in cholesterol homeostasis were detected by real-time PCR and immunoblotting, respectively. Cholesterol efflux was determined from [³H]-cholesterol labeled HPEC and [¹⁴C]-acetate was used as cholesterol precursor to measure cholesterol biosynthesis and esterification. We detected enhanced formation of ROS and of specific, ROS-derived oxysterols in HPEC isolated from GDM versus control pregnancies. ROS-generated oxysterols were simultaneously elevated in cord blood of GDM neonates. Liver-X receptor activation in control HPEC by synthetic agonist TO901319, 7-ketocholesterol, or 7β-hydroxycholesterol upregulated ATP-binding cassette transporters (ABC)A1 and ABCG1 expression, accompanied by increased cellular cholesterol efflux. Upregulation of ABCA1 and ABCG1 and increased cholesterol release to apoA-I and HDL₃ (78 ± 17%, 40 ± 9%, respectively) were also observed in GDM versus control HPEC. The LXR antagonist GGPP reversed ABCA1 and ABCG1 upregulation and reduced the increased cholesterol efflux in GDM HPEC. Similar total cellular cholesterol levels were detected in control and GDM HPEC, while GDM enhanced cholesterol biosynthesis along with upregulated 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol O-acyltransferase 1 (SOAT1) mRNA and protein levels. Our results suggest that in GDM cellular cholesterol homeostasis in the fetoplacental endothelium is modulated via LXR activation and helps to maintain its proper functionality. Copyright © 2018 Elsevier B.V. All rights reserved.
Find related publications in this database (Keywords): GDM; Oxidative stress; Cholesterol metabolism; Oxysterols; Human fetoplacental endothelial cells