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

Item Type:	Article
Title:	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
Creators Name:	Schmid, M. and Sollwedel, A. and Thuere, C. and Wafula, P.O. and Zenclussen, M.L. and Mueller, D.N. and Gratze, P. and Woiciechowsky, C. and Volk, H.D. and Zenclussen, A.C.
Abstract:	It remains arguable if an animal model can be of use in pre-eclampsia (PE) studies, as it is clearly a human disease not observed spontaneously in other species. The aim of this study was to investigate whether PE-like signs in mice inoculated with activated Th1 cells were accompanied by abnormal expression of molecules related to the regulation of blood pressure, viz. nitric oxide synthase enzymes (eNOS and iNOS) and angiotensin (Ang) II receptors (AT1R and AT2R), in order to analyse the relevance of this model for human disease. In this model, C57/BL6-mated BALB/c females received lymphocytes crosslined with anti-CD3 and cultured with interleukin (IL)-2 and IL-12 to mimic PE pathology. Control mice received PBS. eNOS, iNOS and AT1R but not AT2R expression was augmented in the kidneys of PE-mice compared with control pregnant mice. The expression of eNOS but not of iNOS was augmented at the fetal-maternal interface of PE-mice as compared with the controls. NOSs regulate the synthesis of NO, a blood pressure and parturition mediator. As its expression is increased in PE patients, our data suggest that the Th1 cells-induced signs in this model are due to similar mechanisms as in humans. AT1R and AT2R mediate the effect of Ang II, and particularly the AT1R appears to be involved in the pathogenesis of human PE. The increased AT1R expression in the kidneys of PE-mice reinforces the theory that Th1 cells elicit a pathological situation closely resembling the human PE. All together, our data support the use of this animal model to study mechanisms underlying clinically overt PE.
Keywords:	Pre-eclampsia, Murine model, eNOS, AT1R, Th1 cell, Hypertension, Animals, Mice
Source:	Placenta
ISSN:	0143-4004
Publisher:	Elsevier
Volume:	28
Number:	7
Page Range:	688-700
Date:	August 2007
Official Publication:	https://doi.org/10.1016/j.placenta.2006.10.008
PubMed:	View item in PubMed

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