Placenta-derived extracellular vesicles induce preeclampsia in mouse models
Placenta-derived extracellular vesicles induce preeclampsia in mouse models
复制标题
胎盘来源的细胞外囊泡在小鼠模型中诱导先兆子痫
DOI：
10.3324/haematol.2019.226209
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发表时间：
2020-06-01
期刊：
影响因子：
10.1
通讯作者：
Zhang, Jianning
中科院分区：
文献类型：
--
作者：
Han, Cha;Wang, Chenyu;Zhang, Jianning
先兆子痫是一种妊娠引起的疾病，损害母亲的健康，导致妊娠终止或早产。循环中胎盘源性细胞外囊泡（pcEV）水平升高一直与先兆子痫相关，但这些囊泡是否诱发先兆子痫或是否是先兆子痫的产物尚不清楚。在一项小规模的先兆子痫患者队列研究的指导下，我们在小鼠模型中研究了pcEV对先兆子痫发病机制的影响。我们在怀孕的C56 BL/6 J小鼠中检测到pcEV，在交配后17-18天达到峰值水平3.8 +/- 0.9x10（7）/mL。然而，这些怀孕的小鼠只有在注入从受损胎盘中纯化的囊泡后才出现高血压和蛋白尿。这些从受损胎盘释放的细胞外小泡破坏内皮完整性并诱导血管收缩。加强细胞外囊泡的释放可防止细胞外囊泡诱导的小鼠先兆子痫的发生。我们的研究结果表明，pcEV在先兆子痫的因果关系的作用，并确定微血管内皮细胞作为一种新的治疗策略，用于治疗这种妊娠相关的并发症。
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 vesides (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 +/- 0.9x10(7)/mL at 17-18 days postcoitum. 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 dearance of extracellular vesides prevented the development of the extracellular vesicle-induced preeclampsia in mice. Our results demonstrate a causal role of pcEV in preeclampsia and identify microveside dearance as a new therapeutic strategy for the treatment of this pregnancy-associated complication.