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AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase

Item Type:Article
Title:AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase
Creators Name:Dechend, R. and Viedt, C. and Mueller, D.N. and Ugele, B. and Brandes, R.P. and Wallukat, G. and Park, J.K. and Janke, J. and Barta, P. and Theuer, J. and Fiebeler, A. and Homuth, V. and Dietz, R. and Haller, H. and Kreuzer, J. and Luft, F.C.
Abstract:BACKGROUND: We recently identified agonistic autoantibodies directed against the angiotensin AT1 receptor (AT1-AA) in the plasma of preeclamptic women. To elucidate their role further, we studied the effects of AT1-AA on reactive oxygen species (ROS), NADPH oxidase expression, and nuclear factor-kappaB (NF-kappaB) activation. METHODS AND RESULTS: We investigated human vascular smooth muscle cells (VSMC) and trophoblasts, as well as placentas. AT1-AA were isolated from sera of preeclamptic women. Angiotensin II (Ang II) and AT1-AA increased ROS production and the NADPH oxidase components, p22, p47, and p67 phox in Western blotting. We next tested if AT1-AA lead to NF-kappaB activation in VSMC and trophoblasts. AT1-AA activated NF-kappaB. Inhibitor-kappaBalpha (I-kappaBalpha) expression was reduced in response to AT1-AA. AT1 receptor blockade with losartan, diphenylene iodonium, tiron, and antisense against p22 phox all reduced ROS production and NF-kappaB activation. VSMC from p47phox-/- mice showed markedly reduced ROS generation and NF-kappaB activation in response to Ang II and AT1-AA. The p22, p47, and p67 phox expression in placentas from preeclamptic patients was increased, compared with normal placentas. Furthermore, NF-kappaB was activated and I-kappaBalpha reduced in placentas from preeclamptic women. CONCLUSIONS: NADPH oxidase is potentially an important source of ROS that may upregulate NF-kappaB in preeclampsia. We suggest that AT1-AA through activation of NADPH oxidase could contribute to ROS production and inflammatory responses in preeclampsia.
Keywords:AT1 receptors, Pregnancy, Angiotensin, Oxygen, Cells, Antibodies, Animals, Mice
Publisher:American Heart Association
Page Range:1632-1639
Date:1 April 2003
Official Publication:https://doi.org/10.1161/01.CIR.0000058200.90059.B1
PubMed:View item in PubMed

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