Phospholipid Transfer Protein Is Differentially Expressed in Human Arterial and Venous Placental Endothelial Cells and Enhances Cholesterol Efflux to Fetal HDL

Abstract

Phospholipid (PL) 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 local function(s) of PLTP at the fetoplacental endothelium. Because HPEC display morphological and functional diversity when isolated from arteries or veins, we hypothesized that PLTP activity may differ between arterial and venous HPEC. We determined PLTP mRNA and activity levels from isolated HPEC and investigated PLTP-mediated remodeling of fetal HDL particles and their capacity in mediating cholesterol efflux from HPEC. 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 pre-β-mobile HDL particles. Arterial HPEC showed higher Pltp expression levels and secreted PL transfer activity (1.8-fold, P < 0.001) than venous HPEC. In contrast to adult HDL(3), [(3)H]cholesterol efflux to fetal HDL was 21% higher (P < 0.05) from arterial than 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. PLTP mediates PL transfer and participates in reverse cholesterol transport pathways at the fetoplacental barrier. Enhanced cellular cholesterol efflux from HPEC to fetal HDL remodeled by PLTP supports the idea of a local atheroprotective role of PLTP in the placental vasculature.