Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, Div. of Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Sci Rep. 2017 Nov 1;7(1):14807. doi: 10.1038/s41598-017-14926-4.
Normal pregnancy requires adaptations of the maternal vasculature. During preeclampsia these adaptations are not well established, which may be related to maternal hypertension and proteinuria. The effects of preeclampsia on the maternal vasculature are not yet fully understood. We aimed to evaluate gene expression in aortas of pregnant rats with experimental preeclampsia using a genome wide microarray. Aortas were isolated from pregnant Wistar outbred rats with low-dose LPS-induced preeclampsia (ExpPE), healthy pregnant (Pr), non-pregnant and low-dose LPS-infused non-pregnant rats. Gene expression was measured by microarray and validated by real-time quantitative PCR. Gene Set Enrichment Analysis was performed to compare the groups. Functional analysis of the aorta was done by isotonic contraction measurements while stimulating aortic rings with potassium chloride. 526 genes were differentially expressed, and positive enrichment of "potassium channels", "striated muscle contraction", and "neuronal system" gene sets were found in ExpPE vs. Pr. The potassium chloride-induced contractile response of ExpPE aortic rings was significantly decreased compared to this response in Pr animals. Our data suggest that potassium channels, neuronal system and (striated) muscle contraction in the aorta may play a role in the pathophysiology of experimental preeclampsia. Whether these changes are also present in preeclamptic women needs further investigation.
正常妊娠需要母体血管的适应性改变。在子痫前期，这些适应性改变并不完善，这可能与母体高血压和蛋白尿有关。子痫前期对母体血管的影响尚不完全清楚。我们旨在使用全基因组微阵列评估实验性子痫前期孕鼠主动脉中的基因表达。从孕 Wistar 远交大鼠中分离出由低剂量 LPS 诱导的子痫前期（ExpPE）、健康妊娠（Pr）、非妊娠和低剂量 LPS 输注的非妊娠大鼠的主动脉。通过微阵列测量基因表达，并通过实时定量 PCR 进行验证。通过基因集富集分析比较各组。通过等张收缩测量对主动脉进行功能分析，同时用氯化钾刺激主动脉环。526 个基因表达差异，在 ExpPE 与 Pr 相比，“钾通道”、“横纹肌收缩”和“神经元系统”基因集呈阳性富集。与 Pr 动物相比，ExpPE 主动脉环中氯化钾诱导的收缩反应明显降低。我们的数据表明，主动脉中的钾通道、神经元系统和（横纹）肌收缩可能在实验性子痫前期的病理生理学中发挥作用。这些变化是否也存在于子痫前期妇女中还需要进一步研究。
