title: Agonistic antibodies directed at the angiotensin II, AT1 receptor in preeclampsia.
abstract: Immune mechanisms and circulating mediators may be important in the pathogenesis of preeclampsia. We review our findings on agonistic antibodies against the angiotensin II (Ang II) receptor (AT1-AA) and their possible role in the pathogenesis of this disorder. AT1-AA appear in the course of preeclampsia and are largely gone by 6 weeks after delivery. AT1-AA detection relies on a bioassay using spontaneously beating neonatal rat cardiomyocytes. Their specificity has been documented by other methods, including Western blotting, co-localization, and co-immunoprecipitation experiments. AT1-AA induce signaling in vascular cells and trophoblasts including transcription factor activation. The signaling results in tissue factor production and reactive oxygen species 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 proved with certainty. However, we believe the findings are compelling and warrant further study.
authors.affiliation: Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin, Berlin, Germany. dechand@fvk-berlin.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.forename: Volker
authors.initials: V
authors.lastname: Homuth
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Müller
authors.forename: Manja
authors.initials: M
authors.lastname: Krause
authors.forename: Joachim
authors.initials: J
authors.lastname: Dudenhausen
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D002463:Cell Membrane Permeability; D019281:Dimerization; D005260:Female; D006801:Humans; D007163:Immunosorbent Techniques; D009389:Neovascularization, Pathologic; D011225:Pre-Eclampsia / Q000276:immunology* / Q000503:physiopathology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction
chemical_list: D001323:Autoantibodies; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D002118:Calcium