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

Abstract

Preeclampsia is the leading cause of death and morbidity world-wide for the mother and fetus during pregnancy. Preeclampsia does not only effect the mother and the baby during pregnancy, but can also have long-term effects, such as the increase 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 increase 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.

Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta

“…Angiotensin-II binds to this receptor and induces vasoconstrictive activity. Women with PE have increased concentrations of AT1 autoantibodies, sFlt-1, and sEng, and increased sensitivity to angiotensin-II [ 100 ]. sFlt-1 and angiotensin-II levels are significantly increased in preeclamptic rat models, with angiotensin-II promoting sFlt-1 production in response to placental ischemia.…”

Maternal endothelial dysfunction in HIV-associated preeclampsia comorbid with COVID-19: a review

“…However, contradictory studies demonstrate a significant upregulation in oxLDL with reduced concentrations of LOX-1 in PE [ 49 ]. Elevated agonist autoantibodies against angiotensin receptors (AT1-AA) due to placental ischemia enhance Ang II sensitivity via angiotensin II type I receptor (AT1) in PE [ 50 ]. Higher levels of AT1-AA have demonstrated increased placental OS [ 51 ] due to superoxide production through NADPH activation [ 52 ], which may result in vascular injury, deficient trophoblast invasion, placental hypoxia, inflammation, angiogenic imbalance, and reduced bioavailability of NO [ 53 ].…”

Mechanisms of vascular dysfunction in the interleukin-10–deficient murine model of preeclampsia indicate nitric oxide dysregulation

“…Indeed, PE sera contain many vasoactive mediators, including TNF-ɑ, ANGII, stimulating ANGII receptor-1 auto-antibodies (AT1-AA), and ET-1. [30][31][32][33] Vascular reactivity studies demonstrated heightened contractions to phenylephrine and both impaired EDR and, to a lesser extent, EIR in the pregnant IL10 -/-sPE mice. With EDR demonstrating a greater effect, the observed impaired relaxation in this model primarily reflects endothelial dysfunction.…”