From the Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute (H.L., Y.O., E.S., T.C., Y.S.), University of Pittsburgh, PA.
Reproductive Department of Xiangya Hospital, Central South University, Changsha, Hunan, China (H.L.).
Hypertension. 2020 Mar;75(3):762-771. doi: 10.1161/HYPERTENSIONAHA.119.14081. Epub 2020 Jan 27.
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.
虽然先兆子痫是妊娠的一种常见且严重的并发症,但对其病理生理学和诊断的了解却很缺乏。循环血浆外泌体,其中包含 RNA 和其他分子,最近可用于诊断,可能在这方面提供信息。我们检验了这样一个假设,即先兆子痫可能会影响循环母体外周血外泌体中的 miRNA 负荷。我们从 60 名足月孕妇中采集了血浆,其中 20 名孕妇患有先兆子痫,20 名孕妇患有胎儿生长受限,20 名孕妇健康妊娠,作为对照。我们通过连续密度梯度超速离心法从母血浆中分离出外泌体。我们的主要观察变量是外泌体中的 miRNA 负荷,通过定量聚合酶链反应(qPCR)基于 TaqMan 先进 miRNA 检测方法在卡片格式中进行分析,并对同一参与者的全血浆中差异表达的外泌体 miRNA 进行分析。我们发现,在患有先兆子痫的妇女和对照组妇女的外泌体中,有 7 种 miRNA 存在差异表达。相比之下,在胎儿生长受限的妇女和对照组妇女的外泌体 miRNA 表达中没有显著差异。结果不受胎儿性别影响。在全血浆 miRNA 分析中,仅有一种与先兆子痫相关的差异表达的外泌体 miRNA 存在显著差异。我们得出结论,与全血浆 miRNA 不同,从患有先兆子痫的妇女的血浆中提取的外泌体表现出独特的 miRNA 谱,表明血浆外泌体 miRNA 可能为先兆子痫的病理生理学提供深入了解,并可能在疾病诊断中发挥作用。