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Review
. 2018;19(10):781-785.
doi: 10.2174/1389201019666180925121254.

The Role of Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor (AT1-AA) in Pathophysiology of Preeclampsia

Nathan Campbell  1 , Babbette LaMarca  1   2 , Mark W Cunningham Jr  1
Affiliations
Review

The Role of Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor (AT1-AA) in Pathophysiology of Preeclampsia

Nathan Campbell et al. Curr Pharm Biotechnol. 2018.

Abstract

Preeclampsia is the leading cause of death and morbidity worldwide for the mother and fetus during pregnancy. Preeclampsia does not only affect the mother and the baby during pregnancy, but can also have long-term effects, such as the increased risk of hypertension and cardiovascular disease on the offspring and the postpartum mother later in life. The exact cause of preeclampsia is unknown, but women with preeclampsia have elevated concentrations of agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). These AT1-AA's through multiple studies have shown to play a significant role in the pathology and possible genesis of preeclampsia. This review will discuss the discovery of AT1-AAs and the role of AT1-AAs in the pathophysiology of preeclampsia. This review will also discuss future therapeutic approaches towards the AT1-AA to prevent adverse pregnancy outcomes. Furthermore, we will examine the relationship between AT1-AA induced hypertension associated with increased oxidative stress, antiangiogenic factors (such as soluble fms-related tyrosine kinase-1 (sFlt-1), endothelin-1 (ET-1), inflammation, endothelial dysfunction, and reduced renal function. Understanding the pathological role of AT1-AAs in hypertensive pregnancies is important as we search for novel therapies to manage preeclampsia.

Keywords: Preeclampsia; angiotensin II type 1 receptor autoantibody (AT1-AA); endothelin; oxidative stress; renal function..

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Figures

Figure 1
Figure 1. AT1-AA induced hypertension flowchart.
In hypertensive pregnancies, placental ischemia occurs, which increases the production of AT1-AAs. AT1-AAs bind and activate g-coupled AT1 receptors to increase ANGII sensitivity and to stimulate downstream pathways to elevate circulating concentrations endothelin 1, sFlt-1, and ROS that have a pathological effect on the kidney to increase RVR, decrease RBF, and thus decrease GFR (i.e. renal function). Thereby these changes in circulating factors and renal function contribute to hypertension. Abbreviations: AT1-AA, angiotensin II type I receptor antibodies; ANGII, angiotensin II; AT1, angiotensin II type I receptor; sFlt-1, fms-like tyrosine kinase-1; ROS, reactive oxygen species; RVR, renal vascular resistance; RBF, renal blood flow; GFR, glomerular filtration rate.
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