Abstract P193: A Novel Mechanism for the Pathogenesis of Preeclampsia: Cell-Free Mitochondrial DNA Mediated Toll Like Receptor 9 Activation

Abstract

Background: Preeclampsia (PreE) is a significant global health burden which impacts 10 million pregnancies annually resulting in over a half million lost lives. Mitochondrial damage has previously been demonstrated to be present in PreE. A novel relationship may exist between preeclampsia and mitochondrial damage via the release of cell-free mitochondrial DNA (cf-mtDNA). Previous work in models of systemic hypertension shows cf-mtDNA mediated activation of TLR9 to be a key part of disease development. We aim to evaluate the level of TLR9 activation and ROS production in patients with and without PreE. Methods: To investigate whether PreE plasma contains increased levels of cell free DNA that can activate TLR9, HEK-Blue TM -hTLR9 reporter cell line (Invivogen) was treated with 3% plasma from either control or PreE patients. The TLR9 activator ODN2006 served as positive control (Fig.1, A&B). To investigate whether PreE plasma can stimulate production of ROS, HUVECs were treated in similar fashion and ROS was evaluated using Mitosox TM (Fig. 1, C&D). Results: Cells treated with PreE plasma demonstrated a 1.7-fold increase in TLR9 activation vs control (p=0.005, Fig. 1A&B). In addition, Mitosox TM signal indicated a 1.8-fold increase in ROS in PreE vs. control (p=0.066, Fig. 1C&D). Conclusion: We conclude that plasma from PreE patients contains higher levels of cf-mtDNA that stimulates inflammation response via TLR9 that promotes mitochondrial ROS production. This mechanism may present a novel target for treatment of Pre-E.