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(Hypertension. 2007;49:604.)
© 2007 American Heart Association, Inc.

Original Articles, Part 2

Dysregulation of the Circulating and Tissue-Based Renin-Angiotensin System in Preeclampsia

Florian Herse; Ralf Dechend; Nina K. Harsem; Gerd Wallukat; Jürgen Janke; Fatimunnisa Qadri; Lydia Hering; Dominik N. Muller; Friedrich C. Luft; Anne C. Staff

From the Medical Faculty of the Charité (F.H., R.D., J.J., F.Q., L.H., D.N.M., F.C.L.), Franz-Volhard Clinic, HELIOS Klinikum, Berlin, Germany; the Max-Delbrück Center for Molecular Medicine (G.W., D.N.M., F.C.L.), Berlin, Germany; the Department of Obstetrics and Gynecology, Ulleval University Hospital (N.K.H., A.C.S.), and the Faculty of Medicine (N.K.H., A.C.S.), University of Oslo, Oslo, Norway.

Correspondence to Ralf Dechend, Franz Volhard Clinic, Wiltbergstrasse 50, 13125 Berlin, Germany. E-mail ralf.dechend{at}charite.de

The renin-angiotensin system (RAS) participates in preeclampsia; however, the relative contributions from the circulating RAS and the tissue-based, uteroplacental RAS are unknown. We hypothesized that the tissue-based uteroplacental RAS is dysregulated in preeclampsia. We performed microarray and gene expression studies and confirmed the findings on the protein level by immunohistochemistry in ureteroplacental units from 10 preeclamptic women and 10 women with uneventful pregnancies. All of the women were delivered by cesarean section. We also analyzed plasma renin activity and circulating agonistic angiotensin II type 1 (AT₁) receptor autoantibodies. In preeclampsia, we found that the angiotensin II AT₁ receptor gene was 5-fold upregulated in decidua (maternal origin). We also found AT₁ autoantibodies in preeclamptic women and in their offspring by neonatal cardiomyocyte bioassay compared with women with normal pregnancies and their infants (mother: 17.5±2.2 versus 0.05±0.4; fetus: 14.5±1.8 versus 0.5±0.5 bpm). Gene expressions for renin (35.0-fold), angiotensin-converting enzyme (2.9-fold), and angiotensinogen (8.9-fold) were higher in decidua than placenta (fetal origin) in both control and preeclamptic women, whereas the AT₁ receptor was expressed 10-fold higher in placenta than in decidua in both groups. Our findings elucidate the ureteroplacental unit RAS in preeclamptic and normal pregnancies. We found that, in preeclampsia, the AT₁ receptor expression is particularly high in decidua, combined with pregnancy-specific tissue RAS involving decidual angiotensin II production and AT₁ autoantibodies. We also showed that AT₁ autoantibodies cross the ureteroplacental barrier. These components could participate in the pathophysiology of preeclampsia.

Key Words: preeclampsia • renin • angiotensin • AT1 receptor • gene expression • proteomics

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