title: Gestational diabetes mellitus modulates neonatal high-density lipoprotein composition and its functional heterogeneity.
abstract: Gestational diabetes mellitus (GDM) is related to neonatal macrosomia and an increased risk of vascular events. We hypothesized that GDM exerts qualitative effects on neonatal high-density lipoprotein (HDL). HDL was isolated from control (n=11) and GDM maternal/neonatal donors (n=9) and subjected to shotgun proteomics. Differences in HDL mobility were assessed by FPLC and native gel-electrophoresis. Paraoxonase (PON1) activity, cholesterol ester-transfer protein (CETP) mass and activity, phospholipid, triglyceride and cholesterol concentrations were quantified with commercial kits. Total anti-oxidative capacity and cholesterol efflux capability of HDLs were measured. Four proteins involved in lipid metabolism, inflammation and innate immunity were differentially expressed between controls and GDM neonates. ApoM (decreased, p<0.05) and SAA1 (increased, p<0.05) showed the same differences on both, maternal and neonatal GDM HDL. Lower PON1 protein expression was corroborated by lower activity (p<0.05) which in turn was associated with attenuated anti-oxidant capacity of GDM HDL. Protein changes were accompanied by increased levels of triglycerides and decreased levels of cholesterol esters, respectively. The observed differences in GDM HDL lipid moiety may be related to CETP mass and activity alterations. The rate of cholesterol efflux from term trophoblasts to maternal and from placental endothelial cells to neonatal GDM HDL was impaired (p<0.05). In conclusion, GDM causes changes in HDL composition and is intimately associated with impaired cholesterol efflux capability as well as diminished anti-oxidative particle properties. Remodeling of neonatal GDM HDL in utero supports the hypothesis that maternal conditions in pregnancy impact neonatal lipoprotein metabolism.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Austria.
authors.forename: Ivana
authors.initials: I
authors.lastname: Sreckovic
authors.affiliation: Institute of Pathology and Center of Medical Research, Medical University of Graz, Austria; Austrian Center of Industrial Biotechnology, Graz, Austria; Omics Center Graz, Austria.
authors.forename: Ruth
authors.initials: R
authors.lastname: Birner-Gruenberger
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Besenboeck
authors.affiliation: Institute of Medical Biochemistry, Faculty of Pharmacy, Belgrade University, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Miljkovic
authors.affiliation: Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Gunther
authors.initials: G
authors.lastname: Marsche
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Austria.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lang
authors.affiliation: Institute of Medical Biochemistry, Faculty of Pharmacy, Belgrade University, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Kotur-Stevuljevic
authors.affiliation: Institute of Medical Biochemistry, Faculty of Pharmacy, Belgrade University, Serbia.
authors.forename: Zorana
authors.initials: Z
authors.lastname: Jelic-Ivanovic
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Austria. Electronic address: christian.wadsack@medunigraz.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Wadsack
keywords: Anti-oxidative property; GDM; Neonatal HDL