8-iso-Prostaglandin F 2α Increases Expression of LOX-1 in JAR Cells

Abstract

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 F 2α (8-iso-PGF 2α ) 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-PGF 2α could induce the expression of LOX-1 in trophoblastic cells (JAR). We demonstrated augmented cellular uptake of 125 I-tyraminylcellobiose ox-LDL in JAR cells incubated with 8-iso-PGF 2α (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-PGF 2α (10 μmol/L). Incubation with 8-iso-PGF 2α (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-κB binding site demonstrated dose-dependent activation of the reporter gene luciferase after incubation with 8-iso-PGF 2α (0 to 10 μmol/L). We also demonstrated increased accumulation of neutral fats in JAR cells incubated with 8-iso-PGF 2α (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.