Endothelial damage and complement dysregulation in fetuses from pregnancies complicated by preeclampsia.

INTRODUCTION: Our objective was to evaluate the endothelial function profile and complement system in fetuses from preeclamptic pregnancies using ex vivo and in vitro approaches. MATERIAL AND METHODS: A total of 66 singleton pregnancies were prospectively recruited comprising 34 cases of preeclampsia and 32 normotensive pregnancies matched for baseline characteristics. In the ex vivo approach, soluble tumor necrosis factor-a receptor 1 (sTNFR1), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (sVWF), terminal complement complex (sC5b-9), Factor H, complement component C3a and Factor Bb were analyzed in fetal cord blood samples. In the in vitro model, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), Von Willebrand factor (VWF), vascular endothelial cadherin (VE-Cadherin), endothelial nitric oxide synthase (eNOS), reactive oxygen species (ROS) and C5b-9 deposits were evaluated on endothelial cells in culture exposed to fetal sera or plasma. RESULTS: Increased sVCAM-1, sICAM- l and decreased Factor H and Factor Bb concentrations were detected in preeclampsia fetuses as compared to fetuses from normotensive mothers (509.4 ± 28 vs. 378.4 ± 34.3 ng/mL, 161.1 ± 11.9 vs. 114.8 ± 6.8, 199.6 ± 18.3 vs. 267.1 ± 15.4 ng/mL and 6.6 ± 0.7 vs. 10.3 ± 1.4 μg/mL respectively, p < 0.05) with similar results in sTNFR1, sVWF, sC5b-9 and C3a. Endothelial cells exposed to fetal sera from preeclampsia 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 (5 × 10(13) ± 1 × 10(12) vs. 3.5 × 10(13) ± 1.4 × 10(12), p < 0.01) with similar expression of VE-Cadherin and eNOS as compared to those exposed to control fetuses. 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 preeclamptic compared to normotensive mothers (fold change 0.08 ± 0.02 vs. 0.48 ± 0.13, p < 0.01). CONCLUSIONS: High levels of endothelial adhesion molecules and oxidative stress products suggest endothelial damage and reduced in vitro deposition of C5b-9 indicates complement dysregulation in preeclampsia fetuses. More research is necessary to study the impact of preeclampsia on fetal vascular health and innate immunity.