Experimental preeclampsia in rats affects vascular gene expression patterns

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.

The involvement of long noncoding RNA APOA1-AS in the pathogenesis of preeclampsia

“…Based on genetic, immunological, or pharmacological approaches, several animal models have been developed to study placental dysfunction and PE. [40][41][42] The "L-NAME model," first described in 1994, has been used since then according to chronic inhibition of nitric oxide synthase by continuous delivery of L-NAME. 43 L-NAME leads to altered blood pressure and vascular reactivity due to reduced nitric oxide bioavailability.…”

Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats

“…Others have also detected increased markers of SNA in surgical- and environment-induced experimental models of PE. For example, in RUPP dams or administration of lipopolysaccharide (LPS) to pregnant rats, there was an enrichment of genes related to increased neuronal signaling and vasoconstriction in aortic tissue 58 and increased adrenergic receptor-induced vasoconstriction in systemic and renal circulations 59 . Moreover, cold-induced stress reduced mechanisms of placentation and elicited PE symptoms in rats 60 .…”

Placental Microbial Colonization and Its Association With Pre-eclampsia

“…thrombocytopenia, increased anti-angiogenic factors, endothelial dysfunction, and elevated liver enzymes among others (Cotechini et al, 2014;Lip et al, 2017;Li et al, 2019). This implies that the lipopolysaccharide molecule is among the main mediators of PE (Figure 4).…”

“…Lipopolysaccharide from gram-negative bacteria possibly activates TLRs particularly TLR3, TLR4, TLR7, and TLR8, inducing NF-kB (inflammatory mediator), while lipoproteins (LPP) or peptidoglycans from gram-positive bacteria activates TLR2, which leads through a cascade of intermediary steps to NF-kB activation ( Figure 3 ) and thus, collectively initiating the pathogenesis of PE, including abnormal placentation and the maternal syndrome (Cotechini et al, 2014 ; Kell and Kenny, 2016 ). Although reports indicate that only humans are afflicted by PE (McCarthy et al, 2011 ; Xue et al, 2015 ), evidence from experimental animals, using a low dose infusion of lipopolysaccharide, show a pre-eclamptic-like syndrome, which includes hypertension, proteinuria, thrombocytopenia, increased anti-angiogenic factors, endothelial dysfunction, and elevated liver enzymes among others (Cotechini et al, 2014 ; Lip et al, 2017 ; Li et al, 2019 ). This implies that the lipopolysaccharide molecule is among the main mediators of PE ( Figure 4 ).…”