Published Online
on January 8, 2007

A more recent version of this article appeared on March 1, 2007

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Submitted on October 16, 2006
Revised on November 5, 2006

Agonistic Angiotensin II Type 1 Receptor Autoantibodies in Postpartum Women With a History of Preeclampsia

Carl A. Hubel; Gerd Wallukat; Myles Wolf; Florian Herse; Augustine Rajakumar; James M. Roberts; Nina Markovic; Ravi Thadhani; Friedrich C. Luft; and Ralf Dechend^*

From the Magee-Womens Research Institute and Department of Obstetrics and Gynecology and Reproductive Sciences (C.A.H., A.R., J.M.R.), University of Pittsburgh School of Medicine, Pa; the Renal Unit and the Department of Obstetrics and Gynecology (M.W., R.T.), Massachusetts General Hospital, Boston; the Department of Epidemiology (N.M, J.M.R.), University of Pittsburgh Graduate School of Public Health, Pa; the Max-Delbrück Center for Molecular Medicine (G.W.), Berlin, Germany; and the Medical Faculty of the Charité (F.C.L., F.H, R.D), Franz Volhard Clinic, HELIOS Klinikum, Berlin, Germany.

^* To whom correspondence should be addressed. E-mail: ralf.dechend{at}charite.de.

Abstract--Activating angiotensin II type 1 autoantibodies (AT1-AAs) develop in women with preeclampsia and may contribute to the disorder. Insulin resistance and serum concentrations of the antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) are also increased in women with preeclampsia compared with normal pregnancy. sFlt-1 and insulin resistance decrease substantially after delivery; however, significant group differences persist postpartum. Women who have had preeclampsia are at increased cardiovascular risk later in life. We measured AT1-AAs in groups of women with previous preeclampsia (n=29) and previous normal pregnancies (n=35) 18±9 months after the first completed pregnancy. These women had had sFlt-1, insulin resistance homeostasis model assessment score, and related cardiovascular risk factors measured. Activating antibodies were detected by the chronotropic response of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (losartan and prazosin). AT1-AAs were detected in 17.2% of women with previous preeclampsia versus 2.9% of women with previous uncomplicated pregnancies (P<0.05). In contrast, there was no difference in the prevalence of autoantibodies against the 1-adrenoceptor (10% of previous preeclamptic versus 14% of previous normal pregnant). Women with activating autoantibodies had significantly increased sFlt-1, reduced free vascular endothelial growth factor, and higher insulin resistance homeostasis model assessment values compared with autoantibody-negative women. These data suggest that, as with sFlt-1 and insulin resistance, the AT1-AA does not regress completely after delivery and, secondarily, that correlations exist among these variables. The impact of AT1-AA after preeclampsia, especially in the context of cardiovascular risk, remains to be determined.

Key words: angiotensin II • autoantibodies • preeclampsia • pregnancy • soluble vascular endothelial growth factor receptor-1 • insulin resistance • cardiovascular disease

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