Abstract
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.
Highlights
Preeclampsia is a hypertensive pregnancy disorder, which affects 2–8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality[1]
We have shown that the pregnancy-induced changes in endothelial function, such as an increased role of contractile prostaglandins and a decreased role of EDHF in acetylcholine-induced endothelial vasodilation as well as a decreased sensitivity to angiotensin II, were not observed in the preeclamptic rat model[15]
The top 10 we found some interesting genes with regard to possible changes in vascular function, for example Nos[1], Edn[3], and Ang[2] were upregulated in experimental preeclampsia (ExpPE) compared to Pr and Esm[1] was downregulated in ExpPE compared to Pr
Summary
Preeclampsia is a hypertensive pregnancy disorder, which affects 2–8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality[1]. Proinflammatory factors, released by the “diseased” placenta into the maternal circulation, cause a systemic inflammatory response and endothelial cell activation[3]. This together leads to endothelial dysfunction, a hallmark characteristic of preeclampsia[4,5], but possible to an increased risk of developing heart and vascular diseases in preeclamptic women later in life[6,7]. Pregnant rats were infused with a low-dose of LPS resulting in the main characteristics of preeclampsia: an increase in blood pressure, proteinuria, endothelial cell activation and an inflammatory response[16,17,18]. Healthy pregnant (Pr), and control non-pregnant rats (NPr) as well as low-dose LPS-infused non-pregnant rats (NPr + LPS) were used
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