YC-1 reduces placental sFlt-1 and soluble endoglin production and decreases endothelial dysfunction: A possible therapeutic for preeclampsia

• Preeclampsia is a serious complication affecting 5–8% of pregnancies.
• YC-1 reduces sFlt-1 and sENG secretion from primary human tissues.
• It inhibits HIF1α expression in placenta.
• YC-1 reduces endothelial dysfunction.
• YC-1 is a novel potential therapeutic for preeclampsia.

Preeclampsia is a serious complication of pregnancy with no medical treatment. It is caused by intermittent placental hypoxia and release of sFlt-1 and soluble endoglin, leading to wide spread maternal endothelial dysfunction and multisystem organ injury. YC-1 is a guanylyl cyclase activator and HIF1α inhibitor developed for use in hypertension and atherosclerosis. We examined whether YC-1 reduces sFlt-1 and sENG secretion and reverses endothelial dysfunction in primary human tissues. YC-1 significantly reduced sFlt-1 and sENG secretion from human umbilical vein endothelial cells, purified primary trophoblast cells and placental explants taken from patients with preterm preeclampsia. This was concordant with reduced HIF1α expression. YC-1 also reversed TNFα induced endothelial dysfunction, including reduced vascular cell adhesion molecule 1 expression and monocyte adhesion to primary endothelial cells. We conclude YC-1 decreases placental production of sFlt-1 and sENG and decreases endothelial dysfunction. It is a novel therapeutic candidate for preeclampsia.