9 Microarray analysis revealed aorta remodeling during experimental preeclampsia in rat: Animal models

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• 作者：Simone Vivande Lip^a ; Torsten Plö ; sch^a ; Mark V. Boekschoten^b ; Marijke M. Faas^a
• 刊名：Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：6
• 期：3
• 页码：182
• 全文大小：36 K

文摘

Normal pregnancy requires adaptations of the maternal vasculature to ensure healthy fetal and placental development. During preeclampsia these adjustments are not well established, resulting in maternal hypertension and proteinuria. The effects of preeclampsia on the maternal vasculature are not yet fully understood.

Objectives

Compare vascular gene expression pattern during experimental preeclampsia in the rat with healthy pregnant rats using aortic tissue.

Methods

We used our previously established model for preeclampsia. Pregnant Wistar outbred rats were infused with low-dose lipopolysaccharide at day 14 of pregnancy to induce experimental preeclampsia (ExpPE) (n = 5). Control pregnant rats were infused with saline (n = 5) at the same gestational day. At day 20 of pregnancy, the animals were sacrificed and abdominal aortas were isolated. Total aortic RNA was isolated with TRIzol reagent (Invitrogen) and gene expression was measured by GeneChip Rat Gene 1.1 ST arrays (Affymetrix, Santa Clara CA). Gene Set Enrichment Analysis (GSEA) was performed to compare the two groups.

Results

526 Genes were significantly (p-value <0.05 and a fold-change >1.4 or <−1.4) altered in ExpPE compared to healthy pregnant controls. GSEA showed highly significant (p-value <0.001 and a False discovery rate q-value <0.001) positive enrichment in ExpPE, compared to healthy pregnant animals, in potassium channels (Normalized Enrichment Score (NES) = 2.40, mostly contributing genes: Kcna6, Kcnh8 and Hcn4), neuronal system (NES = 2.40, mostly contributing genes: Kcna6, Cacng3, Syn3) and striated muscle contraction (NES = 2.35, mostly contributing genes: Myh8, Tnni1, Myh3) gene sets. Potassium channels are known to play an important role in the establishment of the membrane potential, influencing the depolarization/repolarization of cells which affects the contractility of vascular smooth muscle cells. Vascular smooth muscle cells are also under the control of the autonomic nervous system. Changes in neuronal innervation of the aorta suggest an altered vasodilation/constriction response after neuronal stimuli.

Conclusions

Our data showed that experimental preeclampsia in rats resulted in changes in gene expression levels in the aorta compared to healthy pregnant rats. The data suggest that potassium channels and neuronal innervation in the aorta may play a role in the pathophysiology of experimental preeclampsia. If these changes are also present in preeclamptic women needs to be further investigated.