Page 235 - Haematologica - Vol. 105 n. 6 - June 2020

Placental extracellular vesicles induce preeclampsia
(Figure 2). Lactadherin-/- mice have elevated levels of PS- expressing EV (Figure 3E) and develop hypertension and proteinuria during pregnancy (Figure 3C, D). EV found in lactadherin-/- mice before pregnancy likely come from platelets and endothelial cells, and could further propa- gate endothelial and placental injury, systemic inflamma- tion, and coagulation.32,41 The findings in mice infused with exogenous lactadherin and those deficient in lactad- herin raise several questions, (i) Could insufficient EV clearance induce placenta damage? (ii) Is intrinsically low EV-clearance activity a risk for preeclampsia and, if so, could it serve as a predictive marker? (iii) Could lactad- herin be used as a treatment for preeclampsia? Human plasma contains ~1 ng/mL of lactadherin,42 which may be sufficient during homeostasis, but becomes insufficient to remove a large quantity of microvesicles that are substan-
tially and persistently released during pregnancy, espe- cially in the condition of preeclampsia.
In summary, we demonstrated that pcEV from injured placenta induced a preeclampsia-like condition in mice by inducing endothelial injury, vasoconstriction, and hyper- coagulation. This pcEV-induced condition was prevented by enhancing EV clearance. The rates of pcEV production and clearance could therefore be used for the risk assess- ment of preeclampsia and become new therapeutic tar- gets for preeclampsia.
Funding
This study was supported by National Institutes of Health grants NS087296, HL119391 and HL125957 (to JFD), Natural Science Foundation of China State Key Program grant 81330029 (to JNZ) and research grant 81672399 (to ML).
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