Activating auto-antibodies against the AT1 receptor in preeclampsia.
Immune mechanisms have been shown to be important in the pathogenesis of preeclampsia. Here, we review our studies of agonistic antibodies against the AT1 receptor in the pathogenesis as well as a pathologic phenotype of this disorder, focusing on observations in our laboratory. We have demonstrated their specificity of the binding by Western blotting, co-localization, and co-immunoprecipitation experiments. AT1-AA induce signaling in vascular cells and trophoblasts including AP-1 and nuclear factor-kappaB (NF-kappaB) activation. The signaling results in tissue factor production and reactive oxygen species (ROS) generation, both of which have been implicated in preeclampsia. The role of AT1-AA in preeclampsia and other severe hypertensive conditions has not yet been proven with certainty. However, we believe the findings are compelling and warrant further study.
Dechend
Ralf
R
Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin, Germany. dechend@fvk-berlin.de
Müller
Dominik N
DN
Wallukat
Gerd
G
Homuth
Volker
V
Krause
Manja
M
Dudenhausen
Joachim
J
Luft
Friedrich C
FC
D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1