Angiogenic factors and preeclampsia

Abstract

Preeclampsia is a major cause of maternal and neonatal morbidity and mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, hypertension and proteinuria, may be due to an excess of circulating anti-angiogenic growth factors, most notably soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng). sFlt1 is an endogenous protein that is produced by the placenta. sFlt1 is able to bind to the angiogenic growth factors vascular endothelial growth factor and placental growth factor, thereby neutralizing their functions. High serum concentrations of sFlt1 and low concentrations of free vascular endothelial growth factor and free placental growth factor have been observed during and prior to clinical manifestation of preeclampsia. More recently, serum levels of sEng were also shown to be significantly elevated in preeclamptic women and levels of sEng correlated strongly with disease severity. Therefore, measurement of sFlt1 and sEng in the maternal circulation may be a useful diagnostic and screening tool for preeclampsia. The availability of such a test to predict preeclampsia would have significant impact on current obstetrical care and may help reduce preeclampsia-induced morbidity and mortality. This review will focus on the role of angiogenic factors in normal and abnormal placental development and indicate how measurement of circulating angiogenic factors may help identify women at risk of preeclampsia.