Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia.
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 alpha1-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.
Hubel
Carl A
CA
Magee-Womens Research Institute and Department of Obstetrics and Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pa, USA.
Wallukat
Gerd
G
Wolf
Myles
M
Herse
Florian
F
Rajakumar
Augustine
A
Roberts
James M
JM
Markovic
Nina
N
Thadhani
Ravi
R
Luft
Friedrich C
FC
Dechend
Ralf
R
D000328:Adult; D001323:Autoantibodies; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D009119:Muscle Contraction / Q000276:immunology; D032383:Myocytes, Cardiac / Q000276:immunology; D049590:Postpartum Period; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D018340:Receptors, Adrenergic, alpha-1 / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D001323:Autoantibodies; D007328:Insulin; D044140:Receptor, Angiotensin, Type 1; D018340:Receptors, Adrenergic, alpha-1; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1