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, Ralf Dechend*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

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 α1-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.

Original languageEnglish (US)
Pages (from-to)612-617
Number of pages6
JournalHypertension
Volume49
Issue number3 PART 2 SUPPL.
DOIs
StatePublished - Mar 2007

Keywords

  • Angiotensin II
  • Autoantibodies
  • Cardiovascular disease
  • Insulin resistance
  • Preeclampsia
  • Pregnancy
  • Soluble vascular endothelial growth factor receptor-1

ASJC Scopus subject areas

  • Internal Medicine

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