Mechanism of endogenous digitalis-like factor-induced vascular endothelial cell damage in patients with severe preeclampsia

Abstract

Although endogenous digitalis-like factor (EDLF) is associated with the development of various physical disorders, the role in preeclampsia remains unclear. This study investigated the effects of EDLF on vascular endothelial cell damage in patients with preeclampsia and the potential mechanisms. From July 2014 to July 2015, 120 singleton pregnancy cases underwent a prenatal examination, inpatient delivery and had normal blood pressure were included in the study, either as patients with severe preeclampsia or the control patients. Serum EDLF levels were compared in these two groups, and an in vitro hypoxic trophocyte-induced vascular endothelial cell damage model was established to explore the changes in hypoxic trophocyte EDLF level and the subsequent effects on human umbilical vein endothelial cells (HUVECs). Nuclear factor-κB (NF-κB) p65 gene expression was silenced in hypoxic trophocytes, and EDLF levels and HUVEC damage were subsequently assessed. Serum EDLF levels were signifcantly higher in the severe preeclampsia cases than in the controls at the same gestational week (P<0.001). EDLF levels in hypoxic trophocytes increased with the increasing co-culture duration. Damage to the biofunctions of HUVECs co-cultured with hypoxic trophocytes also increased with co-culture duration. However, silencing of NF-κB p65 in the hypoxic trophocytes reduced the EDLF levels. Annexin A2 was highly expressed in HUVECs, and no biofunctions were significantly damaged (P<0.05) compared with the group without receiving NF-κB p65 silencing. Serum EDLF levels were signifcantly higher in patients with severe preeclampsia compared with the controls. The results of the current study indicate that NF-κB p65 has a role in regulating EDLF production in hypoxic trophocytes.