This Article Full Text Full Text (PDF) All Versions of this Article: 45/4/742    most recent 01.HYP.0000154785.50570.63v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dechend, R. Articles by Müller, D. N. Search for Related Content PubMed PubMed Citation Articles by Dechend, R. Articles by Müller, D. N. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Risk Pregnancy Related Collections Animal models of human disease Other hypertension Hypertension - basic studies Other Vascular biology

(Hypertension. 2005;45:742.)
© 2005 American Heart Association, Inc.

Original Articles

Agonistic Autoantibodies to the AT1 Receptor in a Transgenic Rat Model of Preeclampsia

Ralf Dechend; Petra Gratze; Gerd Wallukat; Erdenechimeg Shagdarsuren; Ralf Plehm; Jan-Hinrich Bräsen; Anette Fiebeler; Wolfgang Schneider; Silvia Caluwaerts; Lisbeth Vercruysse; Robert Pijnenborg; Friedrich C. Luft; Dominik N. Müller

From Medical Faculty of the Charité (R.D., P.G., E.S., R.P., H.-H.B., A.F., W.S., F.C.L.), Franz Volhard Clinic and Department of Pathology, HELIOS-Klinikum Berlin, Germany; Max Delbrück Center for Molecular Medicine (G.W., D.N.M.), Berlin, Germany; and Experimenteel Laboratorium Gynecologie (S.C., L.V., R.P.), Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.

Correspondence to Friedrich C. Luft, Franz Volhard Clinic, Wiltberg Strassse 50, 13125 Berlin, Germany. E-mail luft{at}fvk-berlin.de

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.

Key Words: preeclampsia • rats, transgenic • antibodies • immune systems • renin-angiotensin system

This article has been cited by other articles:

				B. LaMarca, M. Parrish, L. F. Ray, S. R. Murphy, L. Roberts, P. Glover, G. Wallukat, K. Wenzel, K. Cockrell, J. N. Martin Jr, et al. Hypertension in Response to Autoantibodies to the Angiotensin II Type I Receptor (AT1-AA) in Pregnant Rats: Role of Endothelin-1 Hypertension, October 1, 2009; 54(4): 905 - 909. [Abstract] [Full Text] [PDF]

				S. Verlohren, D. N. Muller, F. C. Luft, and R. Dechend Immunology in Hypertension, Preeclampsia, and Target-Organ Damage Hypertension, September 1, 2009; 54(3): 439 - 443. [Full Text] [PDF]

				F. Herse, S. Verlohren, K. Wenzel, J. Pape, D. N. Muller, S. Modrow, G. Wallukat, F. C. Luft, C. W.G. Redman, and R. Dechend Prevalence of Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor and Soluble fms-Like Tyrosine Kinase 1 in a Gestational Age-Matched Case Study Hypertension, February 1, 2009; 53(2): 393 - 398. [Abstract] [Full Text] [PDF]

				B. LaMarca, G. Wallukat, M. Llinas, F. Herse, R. Dechend, and J. P. Granger Autoantibodies to the Angiotensin Type I Receptor in Response to Placental Ischemia and Tumor Necrosis Factor {alpha} in Pregnant Rats Hypertension, December 1, 2008; 52(6): 1168 - 1172. [Abstract] [Full Text] [PDF]

				B. D. LaMarca, J. Gilbert, and J. P. Granger Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia Hypertension, April 1, 2008; 51(4): 982 - 988. [Full Text] [PDF]

				S. Verlohren, M. Niehoff, L. Hering, N. Geusens, F. Herse, A. N. Tintu, A. Plagemann, F. LeNoble, R. Pijnenborg, D. N. Muller, et al. Uterine Vascular Function in a Transgenic Preeclampsia Rat Model Hypertension, February 1, 2008; 51(2): 547 - 553. [Abstract] [Full Text] [PDF]

				Y. Xia, S. M. Ramin, and R. E. Kellems Potential Roles of Angiotensin Receptor-Activating Autoantibody in the Pathophysiology of Preeclampsia Hypertension, August 1, 2007; 50(2): 269 - 275. [Full Text] [PDF]

				C. A. Hubel, G. Wallukat, M. Wolf, F. Herse, A. Rajakumar, J. M. Roberts, N. Markovic, R. Thadhani, F. C. Luft, and R. Dechend Agonistic Angiotensin II Type 1 Receptor Autoantibodies in Postpartum Women With a History of Preeclampsia Hypertension, March 1, 2007; 49(3): 612 - 617. [Abstract] [Full Text] [PDF]

				D Micheloud, L Nuno, M Rodriguez-Mahou, S Sanchez-Ramon, M C Ortega, A Aguaron, E Junco, J Carbone, E Fernandez-Cruz, L Carreno, et al. Efficacy and safety of Etanercept, high-dose intravenous gammaglobulin and plasmapheresis combined therapy for lupus diffuse proliferative nephritis complicating pregnancy Lupus, December 1, 2006; 15(12): 881 - 885. [Abstract] [PDF]

				T. Walther, G. Wallukat, A. Jank, S. Bartel, H.-P. Schultheiss, R. Faber, and H. Stepan Angiotensin II Type 1 Receptor Agonistic Antibodies Reflect Fundamental Alterations in the Uteroplacental Vasculature Hypertension, December 1, 2005; 46(6): 1275 - 1279. [Abstract] [Full Text] [PDF]

				C. Lam, K.-H. Lim, and S. A. Karumanchi Circulating Angiogenic Factors in the Pathogenesis and Prediction of Preeclampsia Hypertension, November 1, 2005; 46(5): 1077 - 1085. [Abstract] [Full Text] [PDF]