Presence of activating autoantibodies against the AT1-Receptor in women with a history of preeclampsia

Activating autoantibodies against G-coupled receptors, especially against the AT1-receptor (AT1R-AA) and the alpha adrenergic receptor have been detected in the serum of patients with preeclampsia. It is not known whether these activating autoantibodies are still present after delivery. If they persist, they might be implicated in the increased cardiovascular risk after preeclampsia. We included 29 normotensive women with a history of preeclampsia and 32 with a history of normal pregnancy during their first completed (nulliparous) pregnancy at 18.0±9.7 months postpartum in the study. The activating antibodies were detected by the chronotropic responses to AT1 receptor–mediated stimulation of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (losartan and prazosin). 17% of former preeclamptic patients and 3% former normal pregnant patients showed a positive bioassay for the AT1-receptor (p<0.05). Activating autoantibodies against the alpha receptor were found in 10% of former normal pregnant and 14.2% of former preeclamptic groups. In an earlier study we had shown that sFLT1, indicating altered angiogenesis, is upregulated in the former preeclamptic group (41.6±6.7 vs. 30.4±10.2; P <0.01). There was no correlation between patients with AT1R-AA and sFLT-1. We are the first to show that AT1R-AA do not disappear after delivery but persists in nearly 20% of former preeclamptic patients. The pathophysiological role of the persistence of AT1R-AA after preeclampsia, especially in the context of an increased cardiovascular risk, remains to be elucidated. Preeclampsia is likely heterogeneous as are the mechanisms of CVD in women with previous preeclampsia with different risk factors. While some appear to express excess sFLT1 postpartum, others appear to demonstrate AT1R-AA. We did not find any correlation between AT1R-AA and sFLT1.