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

Abstract

The Renin-Angiotensin-Aldosterone System (RAAS) is implicated in the pathophysiology of preeclampsia (PE). There is a paucity of data on uteroplacental angiotensin receptors AT1-2 and 4. We evaluated the immunoexpression of AT1R, AT2R, and AT4R within the placental bed of PE vs. normotensive (N) pregnancies stratified by HIV status. Placental bed (PB) biopsies (n = 180) were obtained from N and PE women. Both groups were stratified by HIV status and gestational age into early-and late onset-PE. Immuno-labeling of AT1R, AT2R, and AT4R was quantified using morphometric image analysis. Immunostaining of PB endothelial cells (EC) and smooth muscle cells of spiral arteries (VSMC) displayed an upregulation of AT1R expression compared to the N group (p < 0.0001). Downregulation of AT2R and AT4R expression was observed in PE vs. N group (p = 0.0042 and p < 0.0001), respectively. AT2R immunoexpression declined between HIV+ve and HIV−ve groups, while AT1R and AT4R displayed an increase. An increase in AT1R expression was noted in the EOPE−ve/+ve and LOPE−ve/+ve compared to N−ve/N+ve. In contrast, AT2R and AT4R expression decreased in EOPE−ve/+ve and LOPE-ve/+ve compared to N−ve/N+ve. We demonstrate a significant downregulation of AT2R and AT4R with a concomitant elevated AT1R immunoexpression within PB of HIV-infected PE women. In addition, a decline in AT2R and AT4R with an increase in AT1R immunoexpression in PE, EOPE, and LOPE vs. normotensive pregnancies, irrespective of HIV status. Thus highlighting differential immunoexpression of uteroplacental RAAS receptors based on pregnancy type, HIV status, and gestational age.

Selected haematological markers and C-reactive protein, not AGTR1 SNP, are associated with essential hypertension in Tharaka Nithi County, Kenya

“…Possible future studies could investigate gene expression profiles of AGTR1 among individuals with essential hypertension in Africa which would provide additional data to explore the hypothesis of differing genetic profiles in African populations. Indeed, a recent study on angiotensin receptors (ATR1, ATR2, and ATR4) noted differential AT1R expression in HIV-infected pre-eclamptic women of African descent [39]. Additional studies on the role of other genetic polymorphisms that may be associated with EH in Africa will also need to be conducted to further contribute to a better understanding of the impact of genetics on hypertension in African populations.…”

Renin-angiotensin system in the placenta of women with preeclampsia

“…In the present study, Singh and colleagues in South Africa performed biopsy of the placental bed (PB) in patients with and without PE to determine the expression of AT 1 R, AT 2 R and AT 4 R in PB endothelial cells (EC) and smooth muscle cells (VSMC) by immunostaining [8]. The effect of human immunodeficiency virus (HIV) infection was also examined (Fig.…”