Naslov
Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1

Autori
Štefulj, Jasminka ; Panzenboeck, Ute ; Becker, Tatjana ; Hirschmugl, Birgit ; Schweinzer, Cornelia ; Lang, Ingrid ; Marsche, Gunther ; Sadjak, Anton ; Lang, Uwe ; Desoye, Gernot ; Wadsack, Christian

Izvornik
Circulation research (0009-7330) 104 (2009), 5; 600-608

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
maternal-fetal cholesterol transfer ; endothelial cells ; HDL ; liver X receptors

Sažetak
While maternal-fetal cholesterol transfer may serve to compensate for insufficient fetal cholesterol biosynthesis under pathological conditions, it may have detrimental consequences under conditions of maternal hypercholesterolemia leading to pre-atherosclerotic lesion development in fetal aortas. Maternal cholesterol may enter fetal circulation by traversing syncytiotrophoblast and endothelial layers of the placenta. We hypothesized that endothelial cells (EC) of the feto-placental vasculature display a high and tightly regulated capacity for cholesterol release. Using EC isolated from human term placenta (HPEC), we investigated cholesterol release capacity and examined transporters involved in cholesterol efflux pathways controlled by liver-X-receptors (LXRs). HPEC demonstrated 2.5-fold higher cholesterol release to lipid-free apolipoprotein (apo)A-I than human umbilical vein EC (HUVEC), while both cell types showed similar cholesterol efflux to high-density lipoproteins (HDL). Interestingly, treatment of HPEC with LXR activators increased cholesterol efflux to both types of acceptors, while no such response could be observed for HUVEC. In line with enhanced cholesterol efflux, LXR activation in HPEC increased expression of ATP-binding cassette transporters ABCA1 and ABCG1, while not altering expression of ABCG4 and scavenger receptor class B, type I (SR-BI). Inhibition of ABCA1 or silencing of ABCG1 decreased cholesterol efflux to apoA-I (-70 %) and HDL3 (-57 %), respectively. Immunohistochemistry localized both transporters predominantly to the apical membranes of placental EC in situ. Thus, EC of human term placenta exhibit unique, efficient and LXR-regulated cholesterol efflux mechanisms. We propose a sequential pathway mediated by ABCA1 and ABCG1, respectively, by which HPEC participate in forming mature HDL in the fetal blood.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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