A Narrative Review of the Renin-Angiotensin-Aldosterone System in the Placenta and Placental Bed of HIV Infected Women of African Ancestry with Preeclampsia

Abstract

Purpose of Review Both HIV infection and preeclampsia (PE), a pregnancy-specific disorder of hypertension and multi-system organ involvement, have high prevalence rates especially in low-to-middle-income countries. The immunoexpression of specific renin-angiotensin-aldosterone system (RAAS) receptors in the placenta and placental bed interface may forecast the risk of PE. Recent Findings Preeclampsia is a leading risk factor for mortality worldwide and remains a challenge in HIV-infected individuals especially those on antiretroviral therapy (ART). Irregular RAAS stimulation may be linked to the pathophysiology of hypertension in HIV infection and in PE. The AT1 receptor is expressed across all trimesters of pregnancy, within placental tissue, eliciting vasoconstriction. This increased expression is associated with the severity of PE, implying that the increased expression may be involved in the pathogenesis of this pregnancy disorder. The AT2 receptor expression in normotensive pregnancies was shown to be lower as compared to non-pregnant individuals. Furthermore, in the PE placental bed, the AT2 receptor is the predominant receptor subtype and is found in extravillous trophoblast cells where they facilitate vasodilation. However, AT4R in placentae of PE pregnancies are found to be significantly reduced compared to normotensives pregnancies. Summary The data on the role played by the RAAS pathway in pregnancy is conflicting. Investigation into a tissue-based RAAS with emphasis on immune-expression within the placenta and placental bed may help resolve this conundrum.Keywords Renin-angiotensin-aldosterone system (RAAS) . Preeclampsia . Angiotensin II-type 1 receptor (ATR1) . Angiotensin II-type 2 receptor (ATR2) . Angiotensin II-type 4 receptor (ATR4)This article is part of the Topical Collection on Preeclampsia

Differential expression of the angiotensin receptors (AT1, AT2, and AT4) in the placental bed of HIV-infected preeclamptic women of African ancestry

“…All three trimesters of pregnancy exhibit placental tissue expression of the AT1 receptor [ 20 ]. The severity of PE is correlated with this increased expression, suggesting that the enhanced expression may play a role in the pathophysiology of this pregnancy condition [ 21 – 23 ].…”

Regulation of the Placental Renin-Angiotensin-Aldosterone System in Early- and Late-Onset Preeclampsia

“…It should be noted that the biological properties of angiotensin (AT) II, the main biologically active end product of the RAAS cascade, are diverse and are not limited only to the regulation of vascular tone, which is extremely important during pregnancy. AT II binds to placental receptors and stimulates cell proliferation and migration, angiogenesis, and invasion of trophoblast cells [ 6 ]. Changes in the RAAS are not compensated in women with PE, which leads to capillary constriction, kidney damage, disturbances of water-salt metabolism, etc.…”