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

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2005-12, Vol.46 (6), p.1275-1279
• Main Authors: Walther, Thomas, Wallukat, Gerd, Jank, Alexander, Bartel, Sabine, Schultheiss, Heinz-Peter, Faber, Renaldo, Stepan, Holger
• Format: Article
• Language: English
• Subjects: Adult; Antihypertensive agents; Arterial hypertension. Arterial hypotension; Autoantibodies - blood; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Case-Control Studies; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Endocrine kidney. Renin-angiotensin-aldosterone system; Female; Fetal Growth Retardation - immunology; Fundamental and applied biological sciences. Psychology; Humans; Kidneys; Medical sciences; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Placental Circulation; Pre-Eclampsia - immunology; Pre-Eclampsia - physiopathology; Pregnancy; Pregnancy Trimester, Second - immunology; Pregnancy Trimester, Third - immunology; Receptor, Angiotensin, Type 1 - agonists; Receptor, Angiotensin, Type 1 - immunology; Regional Blood Flow; Urinary system involvement in other diseases. Miscellaneous; Uterus - blood supply; Vertebrates: endocrinology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000190040.66563.04

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.