133. The role of vitamin D in cell-cell interaction of endothelial cells and trophoblasts in a preeclampsia-like model

Abstract

Objective The obstetric history of women is an important part of their cardiovascular risk profile, but also of their offspring. Preeclampsia is a separate, independent risk factor. We hypothesize that fetal endothelial cell functional limitations can already be demonstrated in pregnancies complicated by preeclampsia and that therapeutic use, e.g. with 1.25 (OH)2 Vitamin D3 can balance the negative effects of preeclampsia on cell function. Methods Human umbilical venous endothelial cells (HUVEC) and endothelial colony-forming cells (ECFC) were obtained from umbilical veins and cord blood. Furthermore, a trophoblast cell line (HTR8-SVneo) as well as human uterine venous endothelial cells (HUtMVEC) were available. Serum from uncomplicated and preeclamptic pregnancies was collected. Functional properties such invasion and migration as well as cell interaction of endothelial cells and trophoblasts were investigated with or without 1,25 (OH)2 vitamin D3 treatment. Results In a co-culture and invasion model of HUVEC and ECFC as well as of HUtMVEC and HTR8, the simulation of preeclampsia-like conditions led to a reduced invasion of ECFC or trophoblasts into an endothelial cell monolayer consisting of mature endothelial cells. Vitamin D neutralized the evoked negative effects on functional properties. Furthermore, immunocytochemical studies revealed a cell-cell interaction between immature and mature endothelial cells as well as mature endothelial cells and trophoblasts. Discussion Limited functional capacity of fetal endothelial cells under preeclamptic conditions suggests that pathogenic factors of the dysfunctional placenta adversely affect fetal endothelial cells and thus contribute intracellularly to cellular changes. Physiological concentrations of vitamin D promote important cell functions of endothelial cells. Whether the observed cellular changes persist in the neonatal period and childhood and are a possible early marker of an increased cardiovascular risk of the progeny of preeclamptic pregnancies has to be investigated by further studies.