The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

Placental overproduction of anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) has a key role in the development of preeclampsia (PE). Circulating endothelin-1 (ET-1) levels are also elevated in PE. In this study, we investigated the correlation between ET-1 and sFlt-1, placental growth factor (PlGF), sEng levels during uncomplicated normotensive pregnancy and PE. A total of 218 pregnant primigravid women were enrolled: 110 with PE and 108 uncomplicated normotensive pregnancies. PE was defined as new onset of elevated blood pressure (BP) 4140/ 90mmHg and >= 2+ proteinuria on two occasions after 20 weeks of gestation in previously normotensive pregnant women. Circulating ET-1, sFlt-1, sEng and PlGF levels were estimated using enzyme immunoassays, and correlation between variables was ascertained. Women with PE showed higher levels of sFlt-1 (41.5 +/- 15.7 vs 6.15 +/- 3.4 ng ml(-1), P<0.001), sEng (84.9 +/- 38.8 vs 13.2 +/- 6.3 ng ml-1, P<0.001), ET-1 (1.52 +/- 0.55 vs 0.88 +/- 0.35 pg ml(-1), P<0.001) and sFlt-1: PlGF ratio (591.1 +/- 468.4 vs 18.3 +/- 2.1, P<0.001); and lower levels of PlGF (96.3 +/- 47.2 vs 497.6 +/- 328.2 pg ml(-1), P<0.001). BP levels showed an independent relationship with sFlt1: PlGF ratio in normotensive pregnant women and with sFlt-1: PlGF ratio and ET-1 in PE. sFlt-1 and sFlt-1: PlGF ratio correlated with proteinuria. ET-1 correlated significantly with sFlt-1, sEng and sFlt-1: PlGF ratio in PE. Our results show an association between elevation of sFlt-1 and sEng and ET-1 in the maternal circulation in PE, and strengthen the possibility that ET-1 may be a mediator in genesis of PE syndrome secondary to anti-angiogenic factors released by the placenta. Journal of Human Hypertension (2012) 26, 236-241; doi:10.1038/jhh.2011.29; published online 31 March 2011