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先兆子痫是一种破坏性高血压并发症，发生在妊娠20周后，以新发高血压为特征。这种妊娠特异性综合征是一种严重的妊娠并发症，全球受影响的妊娠人员占比高达5-8%，也是全球妊娠期胎儿和孕产妇发病率和死亡率的主要原因。在患有先兆子痫的妇女中，胎盘抗血管生成因子，包括可溶性fms样酪氨酸激酶-1（soluble Fms-like tyrosine kinase-1，sFlt-1）和可溶内皮糖蛋白（soluble endoglin，sEng）被上调并破坏母体内皮，导致先兆子痫的临床并发症。 此前，同济大学附属第一妇婴保健院的研究人员研究表明，外泌体miRNAs可能对调节血管生成以维持正常妊娠有着重要意义。近日，一项新的研究指出，先兆子痫妊娠中外泌体内容物发生了改变，其外泌体（PE-exo）可以通过向内皮细胞递送sFlt-1和sEng影响血管内皮功能。该研究中，研究人员从来自妊娠年龄匹配的先兆子痫和正常妊娠的血浆样品中分离循环外泌体，采用transwell和matrigel管形成测定样本脐静脉内皮细胞的血管生成。结果显示，来自先兆子痫患者的外泌体表达了丰富的sFlt-1和sEng。考虑到细胞外sFlt和sEng水平转移到人脐静脉内皮细胞的可能性，研究人员又在293细胞中过表达它们并成功地收集含有高水平sFlt-1和sEng的外泌体。结果证明这些外泌体可以减弱体外人脐静脉内皮细胞的增殖、迁移和管形成。在小鼠模型中，来自先兆子痫患者的外泌体也会引起血管功能障碍。 综上，这项研究进一步揭示了外泌体在sFlt-1和sEng转移相关的血管功能障碍中的介导作用，为先兆子痫及其并发症提供潜在干预靶标。 推荐阅读原文：
Exosomes from women with preeclampsia induced vascular dysfunction by delivering sFlt (soluble Fms-like tyrosine kinase)-1 and sEng (soluble endoglin) to endothelial cells.
Preeclampsia is a unique multiple system disorder that affects 5% to 8% of pregnancies. Exosomes, membrane-encapsulated vesicles that are released into the extracellular environment by many cell types, can carry signals to the recipient cells to affect inflammation, apoptosis, and angiogenesis. We hypothesize that exosomes from women with preeclampsia complications impair vascular development by delivering antiangiogenic factors to endothelial cells. In the current study, plasma samples from gestational age-matched preeclampsia and normal pregnancies were used to isolate circulating exosomes by commercial kits. Next, application of transwell and matrigel tube formation assays showed that exosomes from preeclampsia patients impaired angiogenesis of human umbilical vein endothelial cells. We found that exosomes from preeclampsia expressed abundant sFlt-1 (soluble fms-like tyrosine kinase-1) and sEng (soluble endoglin). Considering the possibility that extracellular sFlt and sEng were horizontally transferred to human umbilical vein endothelial cells, we successfully collected exosomes containing high levels of sFlt-1 and sEng by overexpressing them in human embryonic kidney 293 cells. Furthermore, we demonstrated that these exosomes can attenuate the proliferation, migration, and tube formation of human umbilical vein endothelial cells in vitro. In a mouse model, exosomes from preeclampsia patients caused vascular dysfunction directly resulted in adverse preeclampsia-like birth outcomes. Thus, we proposed that exosomes mediated efficient transfer of sFlt-1 and sEng to endothelial cells to damage vascular functions and induce complications in preeclampsia patients.
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