Structural and Functional Characteristics of a Soluble Form of Endoglin in the Context of Preeclampsia

Endoglin is an auxiliary receptor for ligands of TGF-β receptor superfamily, present in endothelial cells and the placental syncytiotrophoblast. The expression of placental membrane endoglin (mEng) is further increased during preeclampsia, a pregnancy-specific hypertensive syndrome. We hypothesize that the soluble form of endoglin (sEng) released from the placenta leads to endothelial dysfunction and hypertension by disrupting normal BMP-9 signaling. We show that cell surface mEng inhibits TGF-β1, BMP-2, and BMP-7 induced Smad1,5,8 phosphorylation while potentiating BMP-9 induced signaling. sEng has been shown to be elevated in the sera of preeclamptic women and is postulated to interfere with endothelial cell function. We show that sEng binds to BMP-9 with a 2 nM affinity and can compete for its binding to endothelial cells, inhibiting downstream Smad1,5,8 phosphorylation. Our results suggest that sEng is contributing to endothelial dysfunction by dysregulating BMP-9 signaling.MAS