Effect of sildenafil citrate on circulating levels of sFlt-1 in preeclampsia.

Abstract

To examine the effect of sildenafil on level of antiangiogenic proteins of preeclampsia. Firstly to examine the effect of sildenafil on serum biomarkers in a patient with preterm preeclampsia. Secondly, to examine the effect of sildenafil on sFlt-1 and soluble endoglin secretion from primary trophoblasts and placental explants. The clinical team administered 50 mg tds sildenafil to a 26-year-old primigravid woman with severe preeclampsia at the threshold of viability (24 3/7 weeks gestation) and we collected bloods to examine the effect of slidenafil on antiangiogenic factors sFlt-1 and soluble endoglin (sENG), pro-angiogenic factor PlGF and vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET1). We administered sildenafil to human primary trophoblasts and placental explants and explored its effect on sFlt-1 and sENG secretion. We examined serum anti-angiogenic factors sFlt-1 and sENG, pro-angiogenic factor PlGF, the potent vasoconstrictor ET1 and VCAM-1 by ELISA. We explored the effect of sildenafil on sFlt-1 secretion from primary trophoblasts and sFlt-1 and sENG secretion from placental explants. We found a reduction in serum sFlt-1, stabilisation in sENG and PlGF in a patient with peri-viable preterm preeclampsia administered oral sildenafil 50 mg three times daily (tds). Furthermore there was an initial stabilisation in serum VCAM-1 and a decline in ET1 with sildenafil administration. This was concordant with stabilisation of clinical and biochemical features of preeclampsia. Interestingly, treating placental cells and tissues in vitro with sildenafil did not appear to change sFlt-1 or sENG secretion. Sildenafil administration was associated with a reduction in serum sFlt-1 and sENG secretion and increase in PlGF secretion in a patient with preterm preeclampsia, potentially via increasing placental perfusion rather than acting directly on the placenta.