(Hypertension. 2001;37:1184.)
© 2001 American Heart Association, Inc.
Scientific Contribution |
8-iso-Prostaglandin F2
Increases Expression of LOX-1 in JAR Cells
From the Institute for Nutrition Research (B.H., A.C.S., T.H., T.R.), Faculty of Medicine, University of Oslo; Departments of Obstetrics and Gynecology (A.C.S.), Aker University Hospital; and Departments of Obstetrics and Gynecology (T.H.), National Hospital, University of Oslo, Norway; and Department of Bioscience (T.S.), National Cardiovascular Center Research Institute, Suita, Osaka, Japan. Dr Halvorsen is currently with the Research Institute for Internal Medicine, National Hospital, University of Oslo, Norway.
Correspondence to Bente Halvorsen, PhD, Research Institute for Internal Medicine, National Hospital, University of Oslo, 0027 Oslo, Norway. E-mail bente.halvorsen{at}klinmed.uio.no
Abstract—Lectinlike
oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized
LDL (ox-LDL), is proposed to be involved in endothelial
dysfunction and in the pathogenesis of atherosclerosis.
Preeclampsia is a pregnancy complication diagnosed by hypertension and
proteinuria, characterized by endothelial dysfunction,
and supposedly caused by compounds from hypoxic uteroplacental tissues.
A feature of preeclampsia is formation of foam cells in maternal
arterial walls of gestational tissue ("acute
atherosis"). Oxidative stress is believed to play a role in the
pathophysiology of preeclampsia. 8-iso-prostaglandin
F2
(8-iso-PGF2) is
a marker of oxidative stress in vivo, is biologically active in vitro,
and is elevated in preeclamptic plasma and gestational tissue. In the
present article, we hypothesized that
8-iso-PGF2 could induce the expression of
LOX-1 in trophoblastic cells (JAR). We demonstrated augmented cellular
uptake of 125I-tyraminylcellobiose ox-LDL in
JAR cells incubated with 8-iso-PGF2 (10
µmol/L) versus control cells. Ligand blots revealed an increased
binding of ox-LDL to LOX-1 in JAR cells incubated with
8-iso-PGF2 (10 µmol/L). Incubation with
8-iso-PGF2 (10 µmol/L) also resulted in
augmented LOX-1 protein levels (Western blots) and mRNA levels
(Northern blots). JAR cells transfected with 3 copies of a nuclear
factor-
B binding site demonstrated dose-dependent activation of the
reporter gene luciferase after incubation with
8-iso-PGF2 (0 to 10 µmol/L). We also
demonstrated increased accumulation of neutral fats in JAR cells
incubated with 8-iso-PGF2 (10 µmol/L) and
ox-LDL compared with controls by oil red O staining. We speculate a
potential role of isoprostanes and LOX-1 in preeclampsia in the
development of "acute atherosis" of gestational spiral
arteries.
Key Words: receptors, lipoprotein • isoprostanes • nuclear factor • trophoblast • preeclampsia
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