EP17.46: Endothelial damage and complement dysregulation in fetuses from pregnancies complicated by pre‐eclampsia

To estimate endothelial function and complement system in fetuses from pre-eclamptic pregnancies using ex vivo and in vitro approaches. 66 singleton pregnancies were prospectively recruited (34 cases of pre-eclampsia and 32 controls matched for baseline characteristics). In the ex vivo approach, soluble TNF-a receptor 1 (sTNFR1), sVCAM-1, sICAM-1, Von Willebrand factor (sVWF), and terminal complement complex (sC5b-9) were analysed in fetal cord blood samples. In the in vitro model, VCAM-1, ICAM-1, Von Willebrand factor (VWF), vascular endothelial cadherin (VE-Cadherin), endothelial nitric oxide synthase (eNOS), radical oxygen species (ROS) and C5b-9 deposits were evaluated on cultured endothelial cells. Increased sVCAM-1, sICAM- l and sTNFR1 concentrations were measured in pre-eclampsia fetuses compared to controls (509.4 ± 28 vs. 378.4 ± 34.3 ng/mL, 161.1 ± 11.9 vs. 114.8 ± 6.8 and 2.5 ± 0.3 vs. 1.5 ± 0.3 ng/mL respectively, p < 0.05) with similar results in sVWF and sC5b-9. Endothelial cells exposed to fetal sera from pre-eclampsia showed incremented expression of VCAM-1 (38.1 ± 1.4% vs. 28.3 ± 1.6%, p < 0.01), ICAM-1 (12 ± 0.9% vs. 8.6 ± 0.6%, p < 0.05), VWF (43.5 ± 2.9% vs. 3.7 ± 0.3%, p < 0.05), and ROS (5x1013±1x1012 vs. 3.5x1013 ± 1.4x1012, p < 0.01) with similar expression of VE-Cadherin and eNOS compared to controls. While soluble C5b-9 was similar between the study groups (851.4 ± 177.5 vs 751.4 ± 132.81 ng/mL, p > 0.05), significantly less C5b-9 deposits on endothelial cells were induced by fetal plasma from pre-eclamptic mothers compared to controls (fold change 0.08 ± 0.02 vs. 0.48 ± 0.13, p < 0.01). High levels of endothelial adhesion molecules and oxidative stress products suggest endothelial damage in fetuses from pre-eclampsia. Additionally, reduced in vitro deposition of C5b-9 indicates complement dysregulation in pre-eclampsia fetuses. More research is warranted to study the impact of pre-eclampsia on fetal vascular health and innate immunity.