Inhibition of Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Protects against Plasma/Hypoxia-Mediated Trophoblast Dysfunction Associated with Preeclampsia

Abstract

Background: Preeclampsia (PE) is associated with oxidative stress in the maternal circulation and placenta. This study aimed to determine if inhibition of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) gives protection against oxidative stress-mediated trophoblast dysfunction. Methods: Plasma and placenta samples were obtained from 106 women with PE and 106 women with normal pregnancy (NP). Oxidized low-density lipoprotein (oxLDL) and soluble LOX-1 levels were determined by enzyme-linked immunoassay. Placental LOX-1 expression was determined by western blotting. Trophoblasts were subjected to hypoxia and treated with pooled plasma from patients with PE. Expression levels of placenta growth factor (PIGF) and the soluble form of the PIGF receptor (sFlt-1) in trophoblasts were determined. Results: Plasma concentrations of oxLDL and sLOX-1 were significantly over-expressed and LOX-1 protein expression in the placenta was significantly increased in PE patients compared with matched NP controls (both p < 0.05). Exposure of trophoblasts to hypoxia and pooled PE plasma induced overexpression of sFlt-1 and downregulation of PIGF. These effects were inhibited by the LOX-1 inhibitor TS20. Conclusion: LOX-1 accumulation may contribute to the pathogenesis of PE by promoting sFlt-1 production in trophoblasts, suggesting that oxidative stress may be an important mediator regulating angiogenic pathways in trophoblasts.