Unique microRNA Signals in Plasma Exosomes from Pregnancies Complicated by Preeclampsia
Unique microRNA Signals in Plasma Exosomes from Pregnancies Complicated by Preeclampsia
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DOI：
10.1161/hypertensionaha.119.14081
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发表时间：
2020-03-01
期刊：
影响因子：
8.3
通讯作者：
Sadovsky, Yoel
中科院分区：
文献类型：
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作者：
Li, Hui;Ouyang, Yingshi;Sadovsky, Yoel
尽管先兆子痫是妊娠常见而严重的并发症，但对其病理生物学和诊断缺乏深入的了解。循环血浆外体含有RNA和其他分子，最近已可用于诊断，在这方面可能是有用的。我们验证了先兆子痫可能影响循环中母体血液外切体中的miRNA货物的假设。我们采集了60例足月妊娠妇女的血浆，其中妊娠合并子痫前期妇女20例，胎儿生长受限妇女20例，正常妊娠妇女20例作为对照。我们用连续密度梯度超速离心法从母体血浆中分离外切体。我们的主要结果变量是外体miRNA Cargo，以卡片形式通过基于定量聚合酶链式反应的TaqMan高级miRNA检测来分析，以及相同参与者的全血浆中差异表达的外体miRNA。我们发现有7种miRNA在子痫前期患者和正常对照的外体中存在差异表达。相比之下，胎儿生长受限妇女和对照组之间外体miRNA的表达没有显著差异。结果不受胎儿性别的影响。在全血浆miRNA分析中，只有一个与子痫前期相关的差异表达的外体miRNAs显著不同。我们的结论是，与全血浆miRNA不同，从子痫前期患者血浆中提取的外切体呈现出独特的miRNA图谱，提示血浆exosomal miRNA可以深入了解子痫前期的病理生理机制，并可能在疾病诊断中发挥作用。
Although preeclampsia is a common and serious complication of pregnancy, insight into its pathobiology and diagnosis is lacking. Circulating plasma exosomes, which contain RNA and other molecules and have recently become accessible for diagnostics, may be informative in this regard. We tested the hypothesis that preeclampsia may affect the miRNA cargo within circulating maternal blood exosomes. We collected plasma from 60 pregnant women at term, including 20 women with pregnancy complicated by preeclampsia, and 20 women with fetal growth restriction and 20 with healthy pregnancy, serving as controls. We isolated exosomes from the maternal plasma by continuous density gradient ultracentrifugation. Our main outcome variable was exosomal miRNA cargo, analyzed by quantitative polymerase chain reaction-based TaqMan advanced miRNA assay in a card format and the expression of differentially expressed exosomal miRNA in whole plasma from the same participants. We found that 7 miRNA species were differentially expressed in exosomes from women with preeclampsia and those from controls. In contrast, there was no significant difference in exosomal miRNA expression between women with fetal growth restriction and controls. The results were not affected by fetal sex. Only one of the preeclampsia-related, differentially expressed exosomal miRNAs was significantly different in whole plasma miRNA analysis. We concluded that unlike whole plasma miRNA, exosomes extracted from the plasma of women with preeclampsia exhibit a unique miRNA profile, suggesting that plasma exosomal miRNA could provide insight into the pathophysiology of preeclampsia, and may play a role in disease diagnostics.