title: Agonistic autoantibodies to the AT1 receptor in a transgenic rat model of preeclampsia.
abstract: We used rats transgenic for the human angiotensinogen (hAogen) gene and the human renin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. The female (n=9) hAogen x male hRen cross had severe (telemetry-measured) hypertension and albuminuria, which developed during the last trimester of pregnancy and subsided after delivery. The converse cross (n=9) and control (n=9) SD rats did not. We demonstrated that the female hAogen x male hRen cross had agonistic antibodies capable of activating the angiotensin (Ang) II AT1 receptor (AT1R-AA) and defined the epitope on the receptor's second extracellular loop. The phenomenon also occurs in humans with preeclampsia. The rats displayed renal histology reminiscent of preeclampsia, including fibrin deposition confined to the glomeruli. The complement system was activated in glomeruli and IgG deposits were present that may represent AT1R-AA. Finally, we observed an atherosis-like lesion in the spiral arteries of the placental bed, which we called placental-bed arteriolosclerosis. Our model may be relevant to preeclampsia in humans.
authors.affiliation: Medical Faculty of the Charité, Franz Volhard Clinic and Department of Pathology, HELIOS-Klinikum Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.forename: Petra
authors.initials: P
authors.lastname: Gratze
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
authors.forename: Erdenechimeg
authors.initials: E
authors.lastname: Shagdarsuren
authors.forename: Ralf
authors.initials: R
authors.lastname: Plehm
authors.forename: Jan-Hinrich
authors.initials: JH
authors.lastname: Bräsen
authors.forename: Anette
authors.initials: A
authors.lastname: Fiebeler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schneider
authors.forename: Silvia
authors.initials: S
authors.lastname: Caluwaerts
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Vercruysse
authors.forename: Robert
authors.initials: R
authors.lastname: Pijnenborg
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Müller
mesh_terms: D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001323:Autoantibodies / Q000276:immunology*; D003167:Complement Activation; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011225:Pre-Eclampsia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists* / Q000276:immunology*; D012083:Renin / Q000235:genetics
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D005337:Fibrin; D012083:Renin