Progress toward identifying potential markers for preeclampsia: role of agonistic autoantibody to the angiotensin II type I receptor.

Abstract

As early as 20 weeks of gestation, preeclamptic women develop new-onset hypertension with proteinuria and display increased circulating factors, ranging from metabolic and proinflammatory to antiangiogenic in nature. These factors have been shown in various experimental models to possibly contribute to the development of hypertension in response to placental ischemia.1–4 A major focus of preeclamptic research has been the identification a molecular marker that could be used to predict early in gestation the development of this disease. Two potential factors associated with the development of preeclampsia are the imbalance of angiogenic factors (vascular endothelial growth factor/placental growth factor) and the antiangiogenic factor (soluble fms-like tyrosine kinase 1 [sFlt-1]), as well as agonistic autoantibody to the angiotensin II type I receptor (AT1-AA).1–5 The AT1-AA has been purified, and specificity for the second extracellular loop of the angiotensin II type I receptor (AT1R) has been demonstrated by Western blotting, colocalization, and coimmunoprecipitation experiments.5 The AT1-AA induces signaling in vascular cells, including activating protein 1, calcineurin, reactive oxygen species, and nuclear factor κB activation, which are blocked by an AT1R antagonist.5–8 In addition, the AT1-AAs appear to be responsible for other effects among different tissues, including stimulation of interleukin 6 production from mesangial cells, and most recently our laboratory has demonstrated AT1-AA activation of the endothelin pathway in human endothelial cells and in …