title: Phospholipid transfer protein is differentially expressed in human arterial and venous placental endothelial cells and enhances cholesterol efflux to fetal HDL.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pathophysiology and Immunology, Medical University of Graz, A-8010 Graz, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Scholler
authors.forename: Christian
authors.initials: C
authors.lastname: Wadsack
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.forename: Anil Paul
authors.initials: AP
authors.lastname: Chirackal Manavalan
authors.forename: Ivana
authors.initials: I
authors.lastname: Sreckovic
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schweinzer
authors.forename: Ursula
authors.initials: U
authors.lastname: Hiden
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
authors.forename: Ute
authors.initials: U
authors.lastname: Panzenboeck
mesh_terms: D000328:Adult; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D021041:Placental Circulation / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D014018:Tissue Distribution; D014471:Umbilical Veins / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D055988:Uterine Artery / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; D002784:Cholesterol