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.