子痫前期患者血浆衍生的细胞外囊泡中血小板和线粒体 RNA 减少：一项探索性研究。
Platelet and mitochondrial RNA is decreased in plasma-derived extracellular vesicles in women with preeclampsia-an exploratory study.
机构信息
Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
Department Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
出版信息
BMC Med. 2023 Nov 23;21(1):458. doi: 10.1186/s12916-023-03178-x.
BACKGROUND
Circulating extracellular vesicles (EVs) are increased in preeclampsia (PE) and are associated with severity and progression. We examined in this exploratory cohort study if the mRNAs and long noncoding RNAs (lncRNAs) in plasma-derived EVs were dysregulated in PE compared to normal pregnancy and display different temporal patterns during gestation.
METHODS
We isolated EVs from plasma at weeks 22-24 and 36-38 in women with and without PE (n=7 in each group) and performed RNA-seq, focusing on mRNAs and lncRNAs. We validated highly expressed mitochondrial and platelet-derived RNAs discovered from central pathways in 60 women with/without PE. We examined further one of the regulated RNAs, noncoding mitochondrially encoded tRNA alanine (MT-TA), in leukocytes and plasma to investigate its biomarker potential and association with clinical markers of PE.
RESULTS
We found abundant levels of platelet-derived and mitochondrial RNAs in EVs. Expression of these RNAs were decreased and lncRNAs increased in EVs from PE compared to without PE. These findings were further validated by qPCR for mitochondrial RNAs MT-TA, MT-ND2, MT-CYB and platelet-derived RNAs PPBP, PF4, CLU in EVs. Decreased expression of mitochondrial tRNA MT-TA in leukocytes at 22-24 weeks was strongly associated with the subsequent development of PE.
CONCLUSIONS
Platelet-derived and mitochondrial RNA were highly expressed in plasma EVs and were decreased in EVs isolated from women with PE compared to without PE. LncRNAs were mostly increased in PE. The MT-TA in leukocytes may be a useful biomarker for prediction and/or early detection of PE.
背景
子痫前期（PE）患者循环细胞外囊泡（EVs）增加，与严重程度和进展相关。本探索性队列研究旨在检测与正常妊娠相比，PE 患者血浆来源 EV 中的 mRNA 和长链非编码 RNA（lncRNA）是否失调，并在妊娠期间呈现不同的时间模式。
方法
我们在 PE 组（n=7）和无 PE 组（n=7）孕妇 22-24 周和 36-38 周时分离 EVs，并进行 RNA-seq，重点关注 mRNAs 和 lncRNAs。我们验证了从中心通路发现的高度表达的线粒体和血小板衍生 RNA。我们进一步检测了 60 名 PE 患者/无 PE 患者中一个调节 RNA，非编码线粒体编码 tRNA 丙氨酸（MT-TA），以研究其生物标志物潜力及其与 PE 临床标志物的关系。
结果
我们发现 EVs 中存在丰富的血小板衍生和线粒体 RNA。与无 PE 组相比，PE 组 EVs 中这些 RNA 的表达降低，lncRNA 增加。通过 qPCR 进一步验证了 EVs 中的线粒体 RNA MT-TA、MT-ND2、MT-CYB 和血小板衍生 RNA PPBP、PF4、CLU。22-24 周时白细胞中 MT-TA 线粒体 tRNA 的表达降低与随后发生的 PE 密切相关。
结论
血小板衍生和线粒体 RNA 在血浆 EVs 中高度表达，与无 PE 组相比，PE 组 EVs 中这些 RNA 的表达降低，lncRNA 主要增加。白细胞中的 MT-TA 可能是预测和/或早期发现 PE 的有用生物标志物。
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