Endothelial dysfunction in the pathogenesis of pre-eclampsia

Abstract

There are many theories regarding the ultimate cause of pre-eclampsia, and nowadays it is thought that the mechanism of pathogenesis is most likely multifactorial. The pathophysiology probably involves both fetal or placental and maternal factors. The most likely relevant factors in the pathogenesis are the abnormal development of the placenta, systemic endothelial dysfunction or cell activation, and an imbalance between pro-angiogenic and anti-angiogenic proteins with a predominance of anti-angiogenic factors. In women with pre-eclampsia, placental tissue overproduces two main anti-angiogenic proteins which enter into the maternal circulation: soluble Fms-such as tyrosine kinase 1 (sFlt1 or sVEGFR1) and soluble endoglin (sEng). Moreover, these patients have low circulating blood levels of two pro-angiogenic peptides: placental growth factor (PlGF) and vascular endothelial growth factor (VEGF). Adequate levels of CECs (circulating endothelial cells), EPCs (endothelial progenitor cells) and microparticles most likely play an important part in the development and regulation of vascularization in pregnancy but the exact role of these cells and micropatticles in the pathogenesis of pre-eclampsia is unknown. Some imbalances in these levels are associated with endothelial insufficiency.