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Selected Publication:
Scholler, M.
Regulation of High-Density Lipoprotein (HDL) Mediated Sterol Transfer Across the Placenta
[ Dissertation ] Medical University of Graz; 2011. pp. 98
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- Authors Med Uni Graz:
- Scholler Monika
- Advisor:
- Desoye Gernot
- Panzenboeck Ute
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- Abstract:
- Phospholipid transfer protein (PLTP) plays a crucial role in high density lipoprotein (HDL) metabolism. In the fetal circulation HDL particles are the main cholesterol-carriers and are involved in maternal-fetal cholesterol transfer across human placental endothelial cells (HPEC). The aim was to investigate the function(s) of PLTP at the feto-placental endothelial barrier. We tested whether PLTP influences fetal HDL remodeling and cellular cholesterol efflux. Since HPEC display a morphological and functional diversity when isolated from arteries or veins, we hypothesized that PLTP activity may differ between arterial and venous HPEC. Furthermore, gestational diabetes mellitus (GDM) causes alterations in fetal HDL composition. Since phospholipid transfer protein (PLTP) is important for HDL (re)assembly we hypothesized that circulating fetal and/or placental PLTP expression and activity is altered in GDM. As determined by native gradient gel electrophoresis, incubation of fetal HDL with active human plasma PLTP resulted in increased particle size (12.6 vs. 13.2 nm, p < 0.05), with a concomitant increase (3.5-fold) in preß-mobile HDL particles, similar to adult HDL3. Placental PLTP was immunolocalized and the endothelium was identified as a major PLTP location. Both, arterial and venous HPEC express and secrete active PLTP. Its phospholipid (PL) transfer activity was higher (1.8-fold, p < 0.001) in arterial than in venous HPEC culture medium. In contrast to adult HDL3, [3H]-cholesterol efflux to fetal HDL was 21 % higher (p < 0.05) from arterial than efflux from venous HPEC. PLTP-facilitated particle conversion increased the cholesterol efflux capacity of fetal HDL to similar extents (55 % and 48 %, p < 0.001) from arterial and venous HPEC, respectively. Placental PLTP expression was up-regulated in GDM (1.8-fold, p < 0.05). PLTP protein (5-fold, p < 0.01) and activity (1.4- to 2.5-fold) were higher in fetal than in maternal serum. Insulin treatment of HPEC significantly increased secreted PLTP levels and activity. In GDM, fetal cholesterol, HDL-triglycerides and phospholipids (PL) were elevated compared to controls. Fetal PLTP activity was higher than maternal but unaltered in GDM. HPEC, arterial more than venous, contribute to the release of active PLTP into the fetal circulation. PLTP may mediate PL transfer and participate in reverse cholesterol transport pathways at the feto-placental barrier. PLTP expression is increased in GDM with hyperglycemia and/or hyperinsulinemia contributing.