Optics and Imaging Centre, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Women's Health and HIV Research Group, Department of Obstetrics and Gynaecology, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Hypertens Res. 2023 Aug;46(8):1970-1982. doi: 10.1038/s41440-023-01314-x. Epub 2023 Jun 12.
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.
肾素-血管紧张素-醛固酮系统（RAAS）与子痫前期（PE）的病理生理学有关。关于胎盘血管紧张素受体 AT1-2 和 4 的数据很少。我们评估了 RAAS 内的 AT1R、AT2R 和 AT4R 在胎盘床中的免疫表达，将其分为 HIV 阳性和正常血压（N）妊娠，并按 HIV 状态分层。从 N 和 PE 女性中获得胎盘床（PB）活检（n=180）。根据 HIV 状态和发病时间将两组分为早发性和晚发性 PE。使用形态计量图像分析定量检测 AT1R、AT2R 和 AT4R 的免疫标记。与 N 组相比，胎盘内皮细胞（EC）和螺旋动脉平滑肌细胞（VSMC）的免疫染色显示 AT1R 表达上调（p<0.0001）。与 N 组相比，PE 组观察到 AT2R 和 AT4R 表达下调（p=0.0042 和 p<0.0001）。在 HIV+ve 和 HIV-ve 组之间，AT2R 免疫表达下降，而 AT1R 和 AT4R 表达增加。与 N-ve/N+ve 相比，EOPE-ve/+ve 和 LOPE-ve/+ve 中 AT1R 表达增加。相反，与 N-ve/N+ve 相比，EOPE-ve/+ve 和 LOPE-ve/+ve 中 AT2R 和 AT4R 表达下降。我们证明了 HIV 感染的 PE 女性的 PB 中 AT2R 和 AT4R 的表达显著下调，同时 AT1R 免疫表达升高。此外，PE、EOPE 和 LOPE 中与正常血压妊娠相比，AT2R 和 AT4R 表达下降，AT1R 免疫表达增加，无论 HIV 状态如何。因此，基于妊娠类型、HIV 状态和孕龄，强调了胎盘 RAAS 受体的不同免疫表达。
