Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.
Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.
复制标题
DOI：
10.3389/fcell.2023.1080419
复制
发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
简介：妊娠血管并发症（GVC），包括妊娠期高血压和先兆子痫，是孕产妇发病和死亡的主要原因。 GVC 中细胞外囊泡 (EV) 水平升高与血管损伤有关。本研究旨在表征 GVC 中的胎盘和循环 EV miRNA，并探讨 EV-miRNA 在 GVC 中的参与，以及它们是否可用于区分胎盘和母体病理。 方法：从 15 名非妊娠 (NP)、18 名健康妊娠 (HP) 和 23 名妊娠晚期患有 GVC 的女性中获取血液样本。剖腹产后获得胎盘切片。对贫血小板血浆 (PPP) 和 EV 颗粒进行了表征：通过纳米颗粒跟踪分析、蛋白质印迹、纳米线技术和 RT-PCR 测量 EV 大小/浓度、蛋白质含量和 miRNA 表达。评估了 EV 对滋养层细胞和 EC miRNA 表达的影响。 结果：与 NP-PPP 相比，HP-PPP 和 GVC-PPP 中观察到较高的 EV 浓度 (p < 0.0001)。与 NP 组相比，HP 和 GVC 的 PPP 和 EV 颗粒中大型 EV（>100 nm）的浓度较高。与 NP-EV 相比，孕妇的 EV 颗粒表现出较低的外泌体标记物 CD63/CD81 表达。 GVC-EV 比 HP-EV 表达更多的人胎盘催乳素 (hPL) 激素，反映了其胎盘起源。对 EV 颗粒和 PPP 中 miRNA 的筛选发现，某些 miRNA 仅在 HP (13%) 和 GVC 组 (15%) 的 EV 颗粒中高表达，但在 NP 组中不表达。检测到 hsa-miR-16-5p、hsa-miR-210 和 hsa-miR-29b-3p 的表达存在差异。 hsa-miR-16-5p 和 hsa-miR-210 的表达在从 NP 获得的 EV 颗粒中较低，在 HP-EV 中较高，在 GVC-EV 中显着较低。除hsa-miR-29b-3p在GVC中表达上调外，胎盘切片中其他miRNA的水平未发现显着差异。与暴露于 HP-EV 的细胞相比，在绒毛滋养层中暴露于 GVC-EV 导致 hsa-miR-29b-3p 表达更高，但在 EC 中则不然。 结论：hsa-miR-16-5p和hsa-miR-210的表达反映母体病理生理状态，而hsa-miR-29b-3p则反映胎盘状态。这些发现表明 EV-miRNA 参与 GVC，并且它们可用于区分先兆子痫中胎盘和母体起源的病理。
Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies. Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated. Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100 nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC. Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.