This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stepan, H. Articles by Walther, T. Search for Related Content PubMed PubMed Citation Articles by Stepan, H. Articles by Walther, T. Related Collections Autoimmunity Female Endocrinology

Relation between Circulating Angiotensin II Type 1 Receptor Agonistic Autoantibodies and Soluble fms-Like Tyrosine Kinase 1 in the Pathogenesis of Preeclampsia

Department of Obstetrics and Gynecology (H.S., R.F.), University of Leipzig, 04109 Leipzig, Germany; Department of Physics (N.W.), University of Potsdam, 14469 Potsdam, Germany; Max-Delbrück Center for Molecular Medicine (G.W.), 13092 Berlin, Germany; Department of Cardiology and Pneumonology (H.-P.S., T.W.), Charité-Campus Benjamin Franklin, 12200 Berlin, Germany; and Department of Pharmacology (T.W.), Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Thomas Walther, Department of Cardiology and Pneumonology, Charité-Universitätsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: thomas.walther{at}charite.de.

Context: Placental and circulatory soluble fms-like tyrosine kinase 1 (sFlt1) has proven to be elevated in pregnant women with preeclampsia, a disease characterized by hypertension, proteinuria, and endothelial dysfunction. Recent studies also demonstrated an autoantibody against the angiotensin II type 1 (AT1) receptor (AT1-AA) in that disease.

Objective: Both factors are discussed as key players in the etiology of preeclampsia. However, it has not yet been clarified whether these two circulating factors correlate and whether synergy determines the severity of pathology.

Design: AT1-AA was retrospectively determined by a bioassay and sFlt1 by an ELISA.

Patients: Serum from second-trimester pregnancies with normal or abnormal uterine perfusion and in women at term with or without pregnancy pathology was analyzed.

Results: Most of the preeclamptic patients were characterized by high sFlt1 levels and the presence of AT1-AA, although the agonistic effects of the antibody did not correlate with the sFlt1 concentrations (P = 0.85). Although AT1-AA was also detected in second-trimester pregnancies evidencing abnormal uterine perfusion without later pathology, sFlt1 was not significantly elevated in these pregnancies, compared with those with normal uterine perfusion. However, whereas women with abnormal perfusion and later pregnancy pathology did not differ in AT1-AA, compared with those with normal outcome, sFlt1 was significantly increased. Again, the two factors did not correlate (P = 0.15).

Conclusions: We conclude that AT1-AA bioactivity and sFlt1 concentrations do not correlate, are not mutually dependent, and are thus probably involved in distinct pathogenetic mechanisms. Both factors in combination may not be causative for the early impaired trophoblast invasion and pathological uterine perfusion.

This article has been cited by other articles:

				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. 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]

				J. S. Gilbert, S. A. Babcock, and J. P. Granger Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats Is Associated With Increased Soluble Fms-Like Tyrosine Kinase-1 Expression Hypertension, December 1, 2007; 50(6): 1142 - 1147. [Abstract] [Full Text] [PDF]