Placenta-derived extracellular vesicles induce preeclampsia in mouse models
Cha Han,
Chenyu Wang,
Yuanyuan Chen,
Jiwei Wang,
Xin Xu,
Tristan Hilton,
Wei Cai,
Zilong Zhao,
Yingang Wu,
Ke Li,
Katie Houck,
Li Liu,
Anil K. Sood,
Xiaoping Wu,
Fengxia Xue,
Min Li,
Jing-fei Dong,
Jianning Zhang
Affiliations
Cha Han
Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China;Bloodworks Research Institute, Seattle, WA, USA
Chenyu Wang
Institute of Pathology, School of Medical Sciences and Gansu Provincial Key Laboratory of Preclinical Study for New Drug Development, Lanzhou University, Lanzhou, China
Yuanyuan Chen
Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China
Jiwei Wang
Department of Neurosurgery, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China
Xin Xu
Bloodworks Research Institute, Seattle, WA, USA
Tristan Hilton
Bloodworks Research Institute, Seattle, WA, USA
Wei Cai
Institute of Pathology, School of Medical Sciences and Gansu Provincial Key Laboratory of Preclinical Study for New Drug Development, Lanzhou University, Lanzhou, China
Zilong Zhao
Department of Neurosurgery, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China
Yingang Wu
Department of Neurosurgery, the First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
Ke Li
Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China
Katie Houck
Bloodworks Research Institute, Seattle, WA, USA
Li Liu
Department of Neurosurgery, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China
Anil K. Sood
Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
Xiaoping Wu
Bloodworks Research Institute, Seattle, WA, USA
Fengxia Xue
Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China
Min Li
Institute of Pathology, School of Medical Sciences and Gansu Provincial Key Laboratory of Preclinical Study for New Drug Development, Lanzhou University, Lanzhou, China
Jing-fei Dong
Bloodworks Research Institute, Seattle, WA, USA;Division of Hematology, Department of Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Jianning Zhang
Department of Neurosurgery, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China
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.
