Murine Pre-Eclampsia Induced by Unspecific Activation of the Immune System Correlates with Alterations in the eNOS and AT1 Receptor Expression in the Kidneys and Placenta

Schmid, Maximilian; Sollwedel, André; Thuere, Catharina; Wafula, Paul Ojiambo; Zenclussen, María Laura; Müller, Dominik N.; Gratze, Petra; Woiciechowsky, Christian; Volk, Hans‐Dieter; Zenclussen, Ana Claudia

doi:10.1016/j.placenta.2006.10.008

Cited by 11 publications

(11 citation statements)

References 43 publications

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“…Researchers have demonstrated that injection of Th1 lymphocytes in order to elicit conditions mimicking the conditions of pre-eclampsia significantly up-regulated AT1R expression in the kidney and placenta [74]. The hypertensive effects have been specifically linked to the renin-angiotensin system, wherein there is an imbalance of vasoconstrictors and vasoactivators, ultimately leading to AngII overwhelming the inherent relaxation mediated by induction of eNOS [75,76] Additionally, catechol o-methyltransferase (COMT) deficient mice are significantly predisposed to pre-eclampsia [77]. Moreover, when these mice are supplemented with 2ME2, the characteristic rise in blood pressure in COMT −/− mice does not occur, establishing that not only 2ME2 restored these knockout mice to control levels, but also made an interesting proposal that 2ME2 may be a physiologically significant metabolite at naturally occurring (i.e.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic Effects of 2-Methoxyestradiol on Angiotensin Type 1 Receptor Down-Regulation in Rat Liver Epithelial and Aortic Smooth Muscle Cells

2012

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Delayed onset of cardiovascular disease among females is not well understood, but could be in part due to the protective effect of estrogen before menopause. Experimental studies have identified the angiotensin type 1 receptor (AT1R) as a key factor in the progression of CVD. In this study, we examined the effects of the estrogen metabolite, 2-methoxyestradiol (2ME2), on AT1R expression. Rat liver cells were exposed to 2ME2 for 24 h and angiotensin II (AngII) binding and AT1R mRNA expressions were assessed. In the presence of 2ME2, cells exhibited significant down-regulation of AngII binding in a dose and time dependent manner, independent of estrogen receptors (ERα/ERβ). Down-regulation of AngII binding was AT1R specific with no change in receptor affinity. Under similar conditions, we observed lower expression of AT1R mRNA, significant inhibition of AngII mediated increase in intracellular Ca2+, and increased phosphorylation of ERK1/2. Pretreatment of cells with the MEK inhibitor PD98059 prevented 2ME2 induced ERK1/2 phosphorylation and down-regulation of AT1R expression, suggesting that the observed inhibitory effect is mediated through ERK1/2 signaling intermediate(s). Similar analyses in stably transfected CHO cell lines with a constitutively active cytomegalovirus (CMV) promoter showed no change in AT1R expression suggesting that 2ME2 mediated effects are through transcriptional regulation. The effect of 2ME2 on AT1R down-regulation through ERK1/2 were consistently reproduced in primary rat aortic smooth muscle cells. As AT1R plays a critical role in the control of cardiovascular diseases, 2ME2-induced changes in receptor expression may provide beneficial effects to the cardiovascular as well as other systems.

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Section: Discussionmentioning

confidence: 99%

Pharmacologic Effects of 2-Methoxyestradiol on Angiotensin Type 1 Receptor Down-Regulation in Rat Liver Epithelial and Aortic Smooth Muscle Cells

2012

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“…In humans, abnormal regulation correlates with a pathologic subendometrial vascular flow index (VFI), and IL-15 levels correlate with high IL-18 levels in sterile patients, but not completely with excess NK counts so that the main effects are likely NK cytotoxic activation rather than replication which seems more strongly correlated to the ratio IL-18/IL-18 BP [33,34]. Experimentally, as stated above injection of high doses of IL-12 or IL-18, or both, produce abortion and /or a pre eclampsia like syndrome in mice [130,171,172].…”

Section: The Role Of the Immune System On Local Vascularizationmentioning

confidence: 93%

Cytokines: Important for implantation?

Chaouat

Dubanchet

Lédée

2007

J Assist Reprod Genet

121

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“…C57/BL6-mated BALB/c females received either 3 ϫ 10 7 Th1-like splenocytes or PBS on gestational days 10 and 12 [preeclampsia (n ϭ 9) and control (n ϭ 13)]. 22,23 Th1-like cell transfer predisposed fetal rejection (Supplemental Figure 1A at http://ajp.amjpathol.org). Blood pressure was measured by a tail cuff method as previously described.…”

Section: Mouse Model Of Preeclampsiamentioning

confidence: 99%

“…Blood pressure was measured by a tail cuff method as previously described. 22,23 On gestational day 14, the mice were sacrificed. Placentae were prepared in paraffin blocks for immunohistochemistry and in Trizol for total RNA isolation.…”

Section: Mouse Model Of Preeclampsiamentioning

confidence: 99%

The Implication of Aberrant GM-CSF Expression in Decidual Cells in the Pathogenesis of Preeclampsia

Huang

Zenclussen

Chen

et al. 2010

The American Journal of Pathology

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Preeclampsia is characterized by an exaggerated systemic inflammatory state as well as shallow placentation. In the decidual implantation site , preeclampsia is accompanied by an excessive number of both macrophages and dendritic cells as well as their recruiting chemokines, which have been implicated in the impairment of endovascular trophoblast invasion. Granulocyte-macrophage colony-stimulating factor is known to regulate the differentiation of both macrophages and dendritic cells, prompting both in vivo and in vitro evaluation of granulocyte-macrophage colony-stimulating factor expression in human decidua as well as in a mouse model of preeclampsia. This study revealed increased granulocyte-macrophage colony-stimulating factor expression levels in preeclamptic decidua. Moreover, both tumor necrosis factor-␣ and interleukin-1 ␤, cytokines that are implicated in the genesis of preeclampsia, markedly up-regulated granulocyte-macrophage colony-stimulating factor production in cultured first-trimester human decidual cells. The conditioned media of these cultures promoted the differentiation of both macrophages and dendritic cells from a monocyte precursor. Evaluation of a murine model of preeclampsia revealed that the decidua of affected animals displayed higher levels of immunoreactive granulocyte-macrophage colony-stimulating factor as well as increased numbers of both macrophages and dendritic cells when compared to control animals. Because granulocyte-macrophage colony-stimulating factor is a potent inducer of differentiation and activation of both macrophages and dendritic cells , these findings suggest that this factor plays a crucial role in the pathogenesis of preeclampsia. (Am J

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Murine Pre-Eclampsia Induced by Unspecific Activation of the Immune System Correlates with Alterations in the eNOS and AT1 Receptor Expression in the Kidneys and Placenta

Cited by 11 publications

References 43 publications

Pharmacologic Effects of 2-Methoxyestradiol on Angiotensin Type 1 Receptor Down-Regulation in Rat Liver Epithelial and Aortic Smooth Muscle Cells

Pharmacologic Effects of 2-Methoxyestradiol on Angiotensin Type 1 Receptor Down-Regulation in Rat Liver Epithelial and Aortic Smooth Muscle Cells

Cytokines: Important for implantation?

The Implication of Aberrant GM-CSF Expression in Decidual Cells in the Pathogenesis of Preeclampsia

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