Soluble endoglin is an accurate predictor and a pathogenic molecule in pre-eclampsia

Abstract

Pre-eclampsia is characterized by new-onset hypertension (>140/90mmHg), proteinuria and oedema after 20 weeks of gestation in previously normotensive, nonproteinuric women. This disease occurs in 5% of pregnancies in the United States and Europe, and can be complicated by renal failure, pulmonary oedema and coagulopathy [1]. Although there has been marked progress toward understanding its pathogenesis, only little advances have been made in prediction and management of pre-eclampsia and it remains a leading cause of maternal and foetal morbidity and mortality worldwide [1]. This editorial is based on an article recently published by the Calcium for Pre-eclampsia Prevention Study Group on the prognostic value of circulating levels of endoglin (Eng) and other angiogenic factors in pre-eclampsia [2]. The study included 72 women who had pre-term pre-eclampsia ( 37 weeks), 120 women with gestational hypertension, 120 normotensive women who delivered infants who were small for gestational age and 120 normotensive controls who delivered infants who were not small for gestational age. They reported that after the onset of clinical disease, the mean circulating soluble endoglin (s-Eng) levels in women with pre-term pre-eclampsia was > four times higher than controls. Beginning at 17 weeks through 20 weeks of gestation, in women in whom pre-term pre-eclampsia later developed, s-Eng levels were significantly higher (about two times) than controls. Increased plasma concentrations of s-Eng was usually accompanied by an increased ratio between plasma concentrations of soluble receptor for Vascular endothetial growth factor (VEGF) fmslike tyrosine kinase 1 (s-FLT1) and the pro-angiogenic protein placental growth factor (PlGF). The risk of pre-eclampsia was greatest among women in the highest quartile of the control distributions for both biomarkers (sEng and sFlt1:PlGF ratio), but not for either biomarker alone. The authors concluded that increased circulating levels of soluble endoglin and ratios of sFlt1:PlGF presage the onset of pre-eclampsia. Elevations in s-Eng were more pronounced and therefore, potentially most useful for prediction, among women in whom pre-term pre-eclampsia developed or women in whom pre-eclampsia developed and who had a smallfor-gestational-age infant. To better understand the meaning of these results, we will briefly revise what is endoglin as well as the function of endoglin in the endothelium.