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

doi:10.3324/haematol.2019.226209

Placenta-derived extracellular vesicles induce preeclampsia in mouse models

Haematologica. 2020 Jun;105(6):1686-1694. doi: 10.3324/haematol.2019.226209. Epub 2019 Aug 22.

Authors

Cha Han^{1

2}, Chenyu Wang³, Yuanyuan Chen¹, Jiwei Wang⁴, Xin Xu², Tristan Hilton², Wei Cai³, Zilong Zhao⁵, Yingang Wu⁶, Ke Li¹, Katie Houck², Li Liu⁵, Anil K Sood⁷, Xiaoping Wu², Fengxia Xue¹, Min Li⁸, Jing-Fei Dong^{9

10}, Jianning Zhang¹¹

Affiliations

¹ Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China.
² Bloodworks Research Institute, Seattle, WA, USA.
³ Institute of Pathology, School of Medical Sciences and Gansu Provincial Key Laboratory of Preclinical Study for New Drug Development, Lanzhou University, Lanzhou, China.
⁴ Department of Neurosurgery, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China.
⁵ Department of Neurosurgery, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China.
⁶ Department of Neurosurgery, the First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
⁷ Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
⁸ Institute of Pathology, School of Medical Sciences and Gansu Provincial Key Laboratory of Preclinical Study for New Drug Development, Lanzhou University, Lanzhou, China limin@lzu.edu.cn.
⁹ Bloodworks Research Institute, Seattle, WA, USA jfdong@bloodworksnw.org.
¹⁰ Division of Hematology, Department of Medicine, University of Washington, School of Medicine, Seattle, WA, USA.
¹¹ Department of Neurosurgery, Tianjin Medical University General Hospital and Tianjin Neurological Institute, Tianjin, China jianningzhang@hotmail.com.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cohort Studies
Disease Models, Animal
Extracellular Vesicles*
Female
Humans
Mice
Placenta
Pre-Eclampsia*
Pregnancy

Abstract

Publication types

MeSH terms

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