What Causes Endothelial Cell Activation in Preeclamptic Women?

Abstract

Preeclampsia is a hypertensive disorder of pregnancy and a leading cause of fetal and maternal morbidity and mortality. It is associated with proteinuria, pathological edema, coagulation abnormalities, reduced uteroplacental blood flow, and intrauterine growth restriction. The cause of preeclampsia is not known, but there is good evidence that it is associated with endothelial cell activation and dysfunction. Many investigators have demonstrated markers of endothelial cell activation in women with preeclampsia. Indicators of endothelial activation include increased circulating levels of von Willebrand factor, endothelin, soluble vascular cell adhesion molecule, thrombomodulin, and cellular fibronectin as well as increased growth factor activity.1,2 Perhaps the most important indicator of endothelial cell dysfunction is decreased plasma and urinary levels of prostacyclin, because the endothelium is the main source of prostacyclin.3–5 Factors present in the blood of preeclamptic women cause endothelial cell activation. For example, exposure of endothelial cells to plasma or serum from preeclamptic women causes activation of nuclear factor-κB and increased expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 compared with plasma or serum from normal pregnant women.6,7 Treatment with antioxidants prevents these effects, so oxidative stress appears to mediate the effects of plasma factors. The question remains what factor or factors present in the blood of preeclamptic women causes endothelial cell activation. To date, a number of possible candidates have been suggested.