Poster Presentation Australasian Extracellular Vesicles Conference 2020

Extracellular vesicles mediate a vicious cycle of poor communication between the placenta and maternal endothelium in preeclampsia. (#55)

Qi Chen 1 , Jing Gao 2 , Yi Sun 2 , Song Peak 1 , Michelle R Wise 1 , Katie Groom 1 , Larry Chamely 1
  1. The University of Auckland, Grafton, Auckland, New Zealand
  2. The Hospital of Obstetrics & Gyanecology, Fudan University, Shanghai, China

Preeclampsia is a life-threatening hypertensive pregnancy disorder. Although the exact pathogenesis of this disease is unclear, it is now well-known that factors, such as extracellular vesicles (EVs) released from preeclamptic placentae into maternal circulation cause systemic endothelial cell dysfunction. Consequently, activated\-endothelial cells prevents the normal adaptation of the maternal vasculature, and induces the symptoms of preeclampsia. We have previously shown both autocrine and paracrine roles for inflammatory cytokines in preeclampsia. Whether EVs also play these two roles in association with endothelial cell dysfunction has not been well investigated. In this study we hypothesise EVs mediate a negative cycle of communication between the placenta and maternal endothelium in preeclampsia.

EVs were isolated from preeclamptic (n=8) and normotensive term placental explants (n=8), and then exposed to endothelial cells (HMEC-1) for 24 hours, which had been labelled with fluorescent dye (CMPTX). The CMPTX-labelled EVs subsequently released from HMEC-1 cells were quantified. EVs released from HMEC-1 that had been previously exposed with preeclamptic EVs were collected and exposed to fresh HMEC-1 for 24 hours. Activation of the fresh HMEC-1 cells was quantified by ELISA for cell surface ICAM-1. In other experiments, EVs were collected from HMEC-1 cells that had been activated with PMA (10 ng/ml), and then exposed to first trimester placental explants in the presence of CMPTX for 24 hours. The CMPTX-labelled EVs subsequently released from placental explants were collected and quantified.

The amount of EVs released from HMEC-1 exposed to preeclamptic EVs was significantly (p<0.05) increased, the amount of EVs released from first trimester placenta exposed to activated-HMEC-1 EVs was significantly increased, compared to controls. EVs released from HMEC-1 cells previously exposed with preeclamptic EVs significantly increased ICAM-1 expression by fresh HMEC-1, compared to controls.

Our data demonstrate EVs from preeclamptic placenta induce endothelial cells to release more EVs which in turn induce more placental EV release and subsequently endothelial cell dysfunction. Although we do not know whether endothelial cell dysfunction is causative or a consequent effect of preeclamptic placental EVs, this data suggests an adverse spiralling interaction between the preeclamptic placenta and maternal endothelium which is mediated in part via EVs.