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(Hypertension. 2005;46:1275.)
© 2005 American Heart Association, Inc.

Original Articles

Angiotensin II Type 1 Receptor Agonistic Antibodies Reflect Fundamental Alterations in the Uteroplacental Vasculature

Thomas Walther; Gerd Wallukat; Alexander Jank; Sabine Bartel; Heinz-Peter Schultheiss; Renaldo Faber; Holger Stepan

From the Department of Cardiology and Pneumology, Charité -Campus Benjamin Franklin, Berlin, Germany (T.W., A.J., H.-P.S.); Department of Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands (T.W.); Max-Delbrück Center for Molecular Medicine, Hindenburgdamm 30, 12200 Berlin, Germany (G.W., S.B.); and Department of Obstetrics and Gynecology, University of Leipzig, Germany (R.F., H.S.).

Reprint requests to Thomas Walther, Department of Cardiology and Pneumology, Charité -Campus Benjamin Franklin, Berlin, Germany. E-mail thomas.walther{at}charite.de

Abnormal uterine perfusion detected by Doppler sonography reflects impaired trophoblast invasion, a factor involved in the pathogenesis of pregnancy complications such as preeclampsia or intrauterine growth retardation. Recent studies have demonstrated an autoantibody against the angiotensin type 1 (AT₁) receptor in pregnant women with preeclampsia. Our aim was to determine whether the AT₁ autoantibody precedes the clinical symptoms and is thus predictive of preeclampsia. We therefore detected this antibody in serum from second trimester pregnancies with abnormal uterine perfusion because these women show an indirect sign of inadequate trophoblast invasion. Then the AT₁ autoantibody distribution/concentration was compared with that of women at term with or without pregnancy pathology. The AT₁ autoantibody was already detectable in second trimester pregnant women with abnormal uterine perfusion before the clinical manifestation of preeclampsia (80%). However, it was also found in second trimester pregnant women with abnormal uterine perfusion who later developed intrauterine growth retardation (60%) or even had a normal course of pregnancy (62%). In the third trimester, the AT₁ autoantibody was demonstrated in 89% of patients with manifest preeclampsia, 86% of those with manifest intrauterine growth retardation, and even in healthy pregnant women at term with a history of abnormal uterine perfusion in the second trimester. We conclude that the AT₁ autoantibody is an early but nonspecific marker for preeclampsia. The generation of this antibody seems to be associated with distinct types of pregnancy disorders resulting from impaired placental development. The AT₁ autoantibody may thus be causative for pathological uteroplacental perfusion.

Key Words: angiotensin II • antibodies • hypertension, gestational • preeclampsia • pregnancy • receptors, angiotensin

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