TY - JOUR AU - Cha Han, AU - Chenyu Wang, AU - Yuanyuan Chen, AU - Jiwei Wang, AU - Xin Xu, AU - Tristan Hilton, AU - Wei Cai, AU - Zilong Zhao, AU - Yingang Wu, AU - Ke Li, AU - Katie Houck, AU - Li Liu, AU - Anil K. Sood, AU - Xiaoping Wu, AU - Fengxia Xue, AU - Min Li, AU - Jing-fei Dong, AU - Jianning Zhang, PY - 2020/06/01 Y2 - 2024/03/29 TI - Placenta-derived extracellular vesicles induce preeclampsia in mouse models JF - Haematologica JA - haematol VL - 105 IS - 6 SE - Articles DO - 10.3324/haematol.2019.226209 UR - https://haematologica.org/article/view/9445 SP - 1686-1694 AB - Preeclampsia is a pregnancy-induced condition that impairs the mother’s health and results in pregnancy termination or premature delivery. Elevated levels of placenta-derived extracellular vesicles (pcEV) in the circulation have been consistently associated with preeclampsia, but whether these vesicles induce preeclampsia or are the product of preeclampsia is not known. Guided by a small cohort study of preeclamptic patients, we examined the impact of pcEV on the pathogenesis of preeclampsia in mouse models. We detected pcEV in pregnant C56BL/6J mice with a peak level of 3.8±0.9×107/mL at 17-18 days post-coitum. However, these pregnant mice developed hypertension and proteinuria only after being infused with vesicles purified from injured placenta. These extracellular vesicles released from injured placenta disrupted endothelial integrity and induced vasoconstriction. Enhancing the clearance of extracellular vesicles prevented the development of the extracellular vesicle-induced preeclampsia in mice. Our results demonstrate a causal role of pcEV in preeclampsia and identify microvesicle clearance as a new therapeutic strategy for the treatment of this pregnancy-associated complication. ER -