title: Distinct composition of human fetal HDL attenuates its anti-oxidative capacity.
abstract: In human high-density lipoprotein (HDL) represents the major cholesterol carrying lipoprotein class in cord blood, while cholesterol is mainly carried by low-density lipoprotein in maternal serum. Additionally, to carrying cholesterol, HDL also associates with a range of proteins as cargo. We tested the hypothesis that fetal HDL carries proteins qualitatively and quantitatively different from maternal HDL. These differences then contribute to distinct HDL functionality in both circulations. Shotgun proteomics and biochemical analyses were used to assess composition/function of fetal and maternal HDL isolated from uncomplicated human pregnancies at term of gestation. The pattern of analyzed proteins that were statistically elevated in fetal HDL (apoE, proteins involved in coagulation, transport processes) suggests a particle characteristic for the light HDL2 sub-fraction. In contrast, proteins that were enriched in maternal HDL (apoL, apoF, PON1, apoD, apoCs) have been described almost exclusively in the dense HDL3 fraction and relevant to its anti-oxidative function and role in innate immunity. Strikingly, PON1 mass and activity were 5-fold lower (p<0.01) in the fetus, which was accompanied by attenuation of anti-oxidant capacity of fetal HDL. Despite almost equal quantity of CETP in maternal and fetal HDL, its enzymatic activity was 55% lower (p<0.001) in the fetal circulation, whereas LCAT activity was not altered. These findings indicate that maternally derived HDL differs from fetal HDL with respect to its proteome, size and function. Absence of apoA-1, apoL and PON1 on fetal HDL is associated with decreased anti-oxidative properties together with deficiency in innate immunity collectively indicating distinct HDLs in fetuses.
authors: Department of Obstetrics and Gynecology, Medical University of Graz, Austria.
authors: Ivana
authors: I
authors: Sreckovic
authors: Ruth
authors: R
authors: Birner-Gruenberger
authors: Britta
authors: B
authors: Obrist
authors: Tatjana
authors: T
authors: Stojakovic
authors: Hubert
authors: H
authors: Scharnagl
authors: Michael
authors: M
authors: Holzer
authors: Monika
authors: M
authors: Scholler
authors: Sonia
authors: S
authors: Philipose
authors: Gunther
authors: G
authors: Marsche
authors: Uwe
authors: U
authors: Lang
authors: Gernot
authors: G
authors: Desoye
authors: Christian
authors: C
authors: Wadsack
mesh_terms: D001053:Apolipoproteins / Q000378:metabolism; D001056:Apolipoproteins C / Q000378:metabolism; D053399:Apolipoproteins D / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D001053:Apolipoproteins; D001056:Apolipoproteins C; D053399:Apolipoproteins D; D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human