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(Hypertension. 2001;37:1184.)
© 2001 American Heart Association, Inc.

Scientific Contribution

8-iso-Prostaglandin F₂ Increases Expression of LOX-1 in JAR Cells

Bente Halvorsen; Anne Cathrine Staff; Tore Henriksen; Tatsuya Sawamura; Trine Ranheim

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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