Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia
Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia
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DOI：
10.3390/ijms21031019
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发表时间：
2020-02-01
影响因子：
5.6
通讯作者：
Wadsack, Christian
中科院分区：
文献类型：
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作者：
Del Gaudio, Ilaria;Sasset, Linda;Wadsack, Christian
具有生物活性的鞘脂正在成为血管功能和体内平衡的关键调节剂。虽然大多数临床研究致力于分析母体血浆中的循环鞘脂，但对鞘脂在胎儿-胎盘血管系统中的作用知之甚少，胎儿-胎盘血管系统与后代循环直接接触。我们的研究旨在比较正常与先兆子痫（PE）胎盘绒毛膜动脉和分离的内皮细胞的鞘脂谱，目的是揭示血管系统中潜在的潜在病理机制。二氢鞘氨醇和鞘磷脂（SM）浓度（C16：0-，C18：0-，和C24：0-鞘磷脂）显着增加绒毛膜动脉先兆子痫胎盘，而总神经酰胺，虽然呈下降趋势，没有统计学差异。此外，RNA和免疫荧光分析显示PE血管中1-磷酸鞘氨醇（S1 P）合成和信号传导受损。我们的数据表明，暴露于一个混乱的母体子宫内环境在PE改变鞘脂签名和基因表达的胎儿侧的胎盘血管。这种病理性重塑包括PE绒毛膜动脉中丝氨酸棕榈酰转移酶（SPT）活性增加和SM累积，伴随这些血管内皮中内皮S1 P信号传导受损。内皮S1 P磷酸酶、裂解酶和S1 PR 2的增加以及S1 PR 1表达的钝化支持绒毛膜动脉中病理表型的发病。
Bioactive sphingolipids are emerging as key regulators of vascular function and homeostasis. While most of the clinical studies have been devoted to profile circulating sphingolipids in maternal plasma, little is known about the role of the sphingolipid at the feto-placental vasculature, which is in direct contact with the offspring circulation. Our study aims to compare the sphingolipid profile of normal with preeclamptic (PE) placental chorionic arteries and isolated endothelial cells, with the goal of unveiling potential underlying pathomechanisms in the vasculature. Dihydrosphingosine and sphingomyelin (SM) concentrations (C16:0-, C18:0-, and C24:0-sphingomyelin) were significantly increased in chorionic arteries of preeclamptic placentas, whereas total ceramide, although showing a downward trend, were not statistically different. Moreover, RNA and immunofluorescence analysis showed impaired sphingosine-1-phosphate (S1P) synthesis and signaling in PE vessels. Our data reveal that the exposure to a deranged maternal intrauterine environment during PE alters the sphingolipid signature and gene expression on the fetal side of the placental vasculature. This pathological remodeling consists in increased serine palmitoyltransferase (SPT) activity and SM accrual in PE chorionic arteries, with concomitance impairment endothelial S1P signaling in the endothelium of these vessels. The increase of endothelial S1P phosphatase, lyase and S1PR2, and blunted S1PR1 expression support the onset of the pathological phenotype in chorionic arteries.