Role of activin A in the pathogenesis of endothelial cell dysfunction in preeclampsia

• We explore the role of activin A & follistatin in the pathogenesis of preeclampsia.
• Activin A & preeclamptic serum up-regulate transcription of ET-1, ICAM-1 and VCAM-1.
• The addition of follistatin mitigates this effect on transcription.
• The activin-binding protein follistatin may be a novel treatment for preeclampsia.

Circulating markers for endothelial activation such as endothelin-1 (ET-1), ICAM-1 and VCAM-1 are elevated in women with preeclampsia. Using human umbilical vein endothelial cells (HUVECs) as an in vitro model of the maternal vasculature, we show that activin A and preeclamptic serum upregulate ET-1, ICAM-1, and VCAM-1 in HUVECs. Further, we show that follistatin, a specific binding protein for activin, mitigates the upregulation of ET-1, ICAM-1 and VCAM-1 in HUVECs exposed to either activin A or preeclamptic serum. These data are consistent with activin A contributing to the pathophysiology of preeclampsia and suggest that therapies targeting activin signalling are worth exploring.