on October 31, 2005
Published online before print October 31, 2005, doi: 10.1161/01.HYP.0000190040.66563.04
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 25, 2005
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.). * To whom correspondence should be addressed. E-mail: thomas.walther{at}charite.de.
Abstract--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.
Revised on September 22, 2005
Angiotensin II Type 1 Receptor Agonistic Antibodies Reflect Fundamental Alterations in the Uteroplacental Vasculature
Thomas Walther*;
Key words: angiotensin II • antibodies • hypertension, gestational • preeclampsia • pregnancy • receptors, angiotensin
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. A. Bainbridge, J.-S. Deng, and J. M. Roberts Increased Xanthine Oxidase in the Skin of Preeclamptic Women Reproductive Sciences, May 1, 2009; 16(5): 468 - 478. [Abstract] [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]
|
|
|
|
 |
|
 L. Anton and K. B. Brosnihan Review: Systemic and uteroplacental renin--angiotensin system in normal and pre-eclamptic pregnancies Therapeutic Advances in Cardiovascular Disease, October 1, 2008; 2(5): 349 - 362. [Abstract] [PDF]
|
|
|
|
|
|
S. A. Karumanchi and M. D. Lindheimer Preeclampsia Pathogenesis: "Triple A Rating"-Autoantibodies and AntiAngiogenic Factors Hypertension, April 1, 2008; 51(4): 991 - 992. [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]
|
|
|
|
|
|
C. C. Zhou, S. Ahmad, T. Mi, S. Abbasi, L. Xia, M.-C. Day, S. M. Ramin, A. Ahmed, R. E. Kellems, and Y. Xia Autoantibody From Women With Preeclampsia Induces Soluble Fms-Like Tyrosine Kinase-1 Production via Angiotensin Type 1 Receptor and Calcineurin/Nuclear Factor of Activated T-Cells Signaling Hypertension, April 1, 2008; 51(4): 1010 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Gilbert, M. J. Ryan, B. B. LaMarca, M. Sedeek, S. R. Murphy, and J. P. Granger Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H541 - H550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xia, C. C. Zhou, S. M. Ramin, and R. E. Kellems Angiotensin Receptors, Autoimmunity, and Preeclampsia J. Immunol., September 15, 2007; 179(6): 3391 - 3395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Ilekis, U. M. Reddy, and J. M. Roberts Review Article: Preeclampsia A Pressing Problem: An Executive Summary of a National Institute of Child Health and Human Development Workshop Reproductive Sciences, September 1, 2007; 14(6): 508 - 523. [Abstract] [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]
|
|
|
|
|
|
H. Stepan and T. Walther Questionable Role of the Angiotensin II Receptor Subtype 1 Autoantibody in the Pathogenesis of Preeclampsia Hypertension, July 1, 2007; 50(1): e3 - e3. [Full Text] [PDF]
|
|
|
|
|
|
R. Dechend Response to Questionable Role of the Angiotensin II Receptor Subtype 1 Autoantibody in the Pathogenesis of Preeclampsia: There Is No Single Universal Preeclampsia Cause Hypertension, July 1, 2007; 50(1): e4 - e4. [Full Text] [PDF]
|
|
|
|
|
|
H. Stepan, A. Unversucht, N. Wessel, and R. Faber Predictive Value of Maternal Angiogenic Factors in Second Trimester Pregnancies With Abnormal Uterine Perfusion Hypertension, April 1, 2007; 49(4): 818 - 824. [Abstract] [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]
|
|
|
|
 |
|
 C. C. Zhou, S. Ahmad, T. Mi, L. Xia, S. Abbasi, P. W. Hewett, C. Sun, A. Ahmed, R. E. Kellems, and Y. Xia Angiotensin II Induces Soluble fms-Like Tyrosine Kinase-1 Release via Calcineurin Signaling Pathway in Pregnancy Circ. Res., January 5, 2007; 100(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Roberts and F. Von Versen-Hoeynck Maternal Fetal/Placental Interactions and Abnormal Pregnancy Outcomes Hypertension, January 1, 2007; 49(1): 15 - 16. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Shibata, R. W. Powers, A. Rajakumar, F. von Versen-Hoynck, M. J. Gallaher, D. L. Lykins, J. M. Roberts, and C. A. Hubel Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E1009 - E1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Stepan, R. Faber, N. Dornhofer, B. Huppertz, A. Robitzki, and T. Walther New Insights into the Biology of Preeclampsia Biol Reprod, May 1, 2006; 74(5): 772 - 776. [Abstract] [Full Text] [PDF]
|
|