Advanced oxidation protein products enhances soluble Fms-like tyrosine kinase 1 expression in trophoblasts: A possible link between oxidative stress and preeclampsia

Abstract

Accumulation of advanced oxidation protein products (AOPPs) is prevalent in obesity, advanced maternal age, diabetes mellitus, and polycystic ovary syndrome. Alterations in the regulation and signaling of angiogenic pathways have been recognized as a link between these conditions and pre-eclampsia. To investigate the possible impact of AOPPs on soluble Fms-like tyrosine kinase 1 (sFlt-1) expression in trophoblasts. A trophoblast cell line (HRT-8/SVneo) was treated with various concentrations of AOPPs. The mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in trophoblasts were measured with the use of real-time polymerase chain reaction; and the secretion of sFlt-1, VEGF, and PlGF protein from trophoblasts were detected with the use of ELISA. Exposure of HRT-8/SVneo cells to AOPPs induced overexpression of sFlt-1 at mRNA and protein levels in a dose dependent manner. These effects could be inhibited by apocynin, an inhibitors of NADPH oxidase. Our data identified AOPPs as a class of important mediator in the regulation and signaling of angiogenic pathways of trophoblasts. Accumulation of AOPPs might contributes to the pathogenesis of preeclampsia by promoting sFlt-1 production in trophoblasts.