Sonographic Flow-Mediated Dilation Imaging versus Electronic EndoCheck Flow-Mediated Slowing by VICORDER in Pregnant Women-A Comparison of Two Methods to Evaluate Vascular Function in Pregnancy.

The evaluation of endothelial function is gaining interest and importance during pregnancy, since the impaired adaptation in early pregnancy has been associated with an increased risk in preeclampsia and fetal growth restriction. To standardize the risk assessment and to implement the evaluation of vascular function in routine pregnancy care, a suitable, accurate and easy to use method is needed. Flow-mediated dilatation (FMD) of the brachial artery assessed by ultrasound is considered to be the gold standard for measuring the vascular endothelial function. The challenges of the FMD measurement have so far prevented its introduction into clinical routine. The VICORDER® device allows an automated determination of the flow-mediated slowing (FMS). The equivalence of FMD and FMS has not yet been proven in pregnant women. We collected data of 20 pregnant women randomly and consecutively while they presented for a vascular function assessment in our hospital. The gestational age at investigation was between 22 and 32 weeks of gestation, three had preexisting hypertensive pregnancy disease and three were twin pregnancies. The results for FMD or FMS below 11.3% were considered to be abnormal. Comparing FMD to FMS results in our cohort revealed a convergence in 9/9 cases, indicating normal endothelial function (specificity of 100%) and a sensitivity of 72.7%. In conclusion, we verify that the FMS measurement is a convenient, automated and operator-independent test method of endothelial function in pregnant women.

PETN-Induced Antioxidative Properties in Endothelial Cells as a Target for Secondary Prevention of Endothelial Dysfunction in Pregnancy.

The NO-donor Pentaerytrithyltetranitrate (PETN) has vasodilatative properties and direct protective effects on endothelial cells. We formerly demonstrated that PETN, given to pregnant women during the second and third trimester, influences endothelial dysfunction related pregnancy complications like preeclampsia (PE) and fetal growth restriction (FGR). PETN treatment showed to delay PE to late pregnancy and achieved a profound risk reduction for FGR and/or perinatal death of 40%. The aim of this study was to confirm the effect of PETN on endothelial cell dysfunction at molecular level in an experimental approach. To induce endothelial dysfunction HUVEC were treated with 10 U/l of thrombin in the presence or absence of PETN. qRT-PCR analysis showed that PETN induced the expression of heme-oxygenase-1 and superoxide dismutase two but not endothelial NO-synthase under basal conditions. The induction of antioxidant proteins did not change basal reactive oxygen species (ROS) levels as measured by MitoSOX™ staining. PETN treatment significantly delayed the thrombin-induced disruption of the endothelial monolayer, determined using the xCELLigence® and attenuated the disrupting effect of thrombin on tubular junctions as seen in a tube-forming assay on Matrigel™. In western-blot-analysis we could show that PETN significantly reduced thrombin-induced extracellular signal-regulated kinase activation which correlates with reduction of thrombin-induced ROS. These experimental results establish the concept of how PETN treatment could stabilize endothelial resistance and angiogenic properties in pregnancy-induced stress. Thus, our results underscore the assumption, that the shown clinical effects of PETN are associated to its endothelial cell protection.