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

Research paper by Fiona C FC Brownfoot, Stephen S Tong, Natalie J NJ Hannan, Roxanne R Hastie, Ping P Cannon, Laura L Tuohey, Tu'uhevaha J TJ Kaitu'u-Lino

Indexed on: 15 Jul '15Published on: 15 Jul '15Published in: Molecular and Cellular Endocrinology


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.

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