Institute of Pathophysiology and Immunology, Medical University of Graz, A-8010 Graz, Austria.
J Clin Endocrinol Metab. 2012 Jul;97(7):2466-74. doi: 10.1210/jc.2011-2969. Epub 2012 Apr 6.
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.
磷脂转移蛋白（PLTP）在高密度脂蛋白（HDL）代谢中起着至关重要的作用。在胎儿循环中，HDL 颗粒是胆固醇的主要载体，并参与了母体-胎儿胆固醇在人胎盘内皮细胞（HPEC）中的转运。
本研究旨在探讨 PLTP 在胎-胎盘内皮的局部功能。由于 HPEC 从动脉或静脉分离时表现出形态和功能的多样性，我们假设 PLTP 活性可能在动脉和静脉 HPEC 之间存在差异。
我们测定了分离的 HPEC 中的 PLTP mRNA 和活性水平，并研究了 PLTP 介导的胎儿 HDL 颗粒的重塑及其介导胆固醇从 HPEC 流出的能力。
用活性人血浆 PLTP 孵育胎儿 HDL 会导致颗粒大小增加（12.6 对 13.2nm，P < 0.05），同时前-β-迁移性 HDL 颗粒增加（3.5 倍）。动脉 HPEC 表现出更高的 Pltp 表达水平和分泌的 PL 转移活性（1.8 倍，P < 0.001）比静脉 HPEC。与成人 HDL（3）相比，[（3）H]胆固醇从动脉 HPEC 向胎儿 HDL 的流出率高 21%（P < 0.05）。PLTP 促进的颗粒转化增加了胎儿 HDL 的胆固醇流出能力，从动脉和静脉 HPEC 分别增加了 55%和 48%（P < 0.001）。
PLTP 介导 PL 转移，并参与胎-胎盘屏障的胆固醇逆转运途径。PLTP 重塑的胎儿 HDL 增强了 HPEC 的细胞胆固醇流出，支持 PLTP 在胎盘血管中具有局部抗动脉粥样硬化作用的观点。
