15-OR

Abstract

Objectives There is a growing body of evidence indicating that mitochondrial dysfunction is a pathogenic mediator of oxidative stress in preeclampsia and can modulate the clinical characteristics of the syndrome. The health of mitochondria is in part mediated by their biogenesis. The inducible transcriptional co-activator peroxisome proliferator activated receptor γ co-activator 1- α (PGC-1 α ) is a well characterized pleiotropic orchestrator of mitochondrial biogenesis and homeostasis. Furthermore, PGC-1 α is a powerful regulator of ROS metabolism. Aim: To investigate the role of mitochondrial-specific ROS in coordinating vascular dysfunction in pre-eclampsia. Methods HUVEC were cultured for 24 hours with 3% pooled plasma from women with preeclampsia ( n = 6) and matched controls with uncomplicated pregnancies ( n = 6) from the SCOPE ( www.scopestudy.net ) biobank. Mitochondrial-specific superoxide was detected by fluorescent microscopy of MitoSOX probe upon its oxidation by mitochondrial O2−. The expression profile of PGC-1 α and its target genes SOD2, HO-1 and mitochondrial uncoupling protein UCP-1 were evaluated by real-time PCR. Markers of endothelial activation including endothelin-1 were measured by real-time PCR. Results Levels of plasma-induced mitochondrial superoxide production were increased in endothelial cells incubated with plasma from women with pre-eclampsia compared with matched controls (15.28 vs. 11.32 MFI, P ⩽ 0.01). The expression of PGC-1 α (1 vs. 1.5 ± 0.19 fold, P P P Conclusions Mitochondrial superoxide regulates plasma mediator-induced endothelial dysfunction in pre-eclampsia. The concurrent increase in PGC-1 α expression may co-ordinate a potential protective response to the elevation in mitochondrial ROS through the induction of uncoupling protein antioxidants. Disclosures C. McCarthy: None. L.C. Kenny: None.