Optics and Imaging Centre, Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Department of Obstetrics and Gynaecology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Histochem Cell Biol. 2024 Nov 23;163(1):8. doi: 10.1007/s00418-024-02341-6.
Preeclampsia, a severe pregnancy complication linked to defective placentation, poses significant maternal risks and is characterized by dysregulated angiogenic factors, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Women with HIV/AIDS and receiving ART may face an increased susceptibility to preeclampsia development due to immunological and angiogenic imbalance. This study investigates the immunoexpression of these factors in the context of HIV-associated preeclampsia, utilizing morphometric image analysis. The study cohort comprised 180 women, including 60 normotensive and 120 preeclamptic participants, further stratified by HIV status and gestational age (early-onset PE [EOPE] < 34 weeks and late-onset PE [LOPE] ≥ 34 weeks). Placental bed tissues were immunostained with mouse anti-human sFlt-1 and PlGF antibodies, and the results were analyzed using Zeiss Axio-Vision and GraphPad Prism software. sFlt-1 levels showed no significant overall difference between preeclamptic and normotensive women (p = 0.8661), though slightly increased in the preeclamptic myometrium, independent of HIV status. However, sFlt-1 levels were significantly higher in EOPE compared to both normotensive and LOPE groups. PlGF immunostaining also showed no significant overall difference (p = 0.7387) but was notably lower in preeclamptic pregnancies and significantly higher in EOPE compared to LOPE. HIV status did not significantly impact sFlt-1 or PlGF levels, although sFlt-1 was slightly higher in HIV-negative women, while PlGF was marginally higher in HIV-positive women. These findings highlight the complex role of angiogenic factors in preeclampsia pathophysiology and suggest that antiretroviral therapies (ARTs) may contribute to the dysregulation of these factors due to a heightened immune milieu.
子痫前期是一种严重的妊娠并发症,与胎盘功能不全有关,会给产妇带来严重风险,其特征是血管生成因子失调,包括胎盘生长因子 (PlGF) 和可溶性 fms 样酪氨酸激酶-1 (sFlt-1)。感染人类免疫缺陷病毒 (HIV) 并接受抗逆转录病毒治疗 (ART) 的女性可能由于免疫和血管生成失衡而更容易发生子痫前期。本研究利用形态计量图像分析,探讨了这些因子在 HIV 相关子痫前期中的免疫表达。研究队列包括 180 名女性,其中 60 名血压正常,120 名子痫前期患者,进一步根据 HIV 状态和孕龄(早发型子痫前期 [EOPE] < 34 周和晚发型子痫前期 [LOPE] ≥ 34 周)进行分层。用鼠抗人 sFlt-1 和 PlGF 抗体对胎盘床组织进行免疫染色,使用 Zeiss Axio-Vision 和 GraphPad Prism 软件进行分析。sFlt-1 水平在子痫前期和血压正常的女性之间没有显著差异(p = 0.8661),但子痫前期的子宫肌层略有增加,与 HIV 状态无关。然而,EOPE 组的 sFlt-1 水平明显高于血压正常组和 LOPE 组。PlGF 免疫染色也没有显著差异(p = 0.7387),但子痫前期妊娠的 PlGF 水平明显较低,EOPE 组明显高于 LOPE 组。HIV 状态对 sFlt-1 或 PlGF 水平没有显著影响,尽管 HIV 阴性女性的 sFlt-1 略高,而 HIV 阳性女性的 PlGF 略高。这些发现强调了血管生成因子在子痫前期病理生理学中的复杂作用,并提示抗逆转录病毒治疗 (ART) 可能由于免疫环境的改变而导致这些因子失调。