Chandra Neelima, Kimble Thomas D, Heim Kathleen R, Anderson Sharon M, Wong Andrew P, Thurman Andrea R, Doncel Gustavo F
CONRAD, Eastern Virginia Medical School, Old Dominion University, Norfolk, VA, United States.
Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, United States.
Front Reprod Health. 2025 Aug 11;7:1587699. doi: 10.3389/frph.2025.1587699. eCollection 2025.
Preeclampsia (PE) is a complex multisystem disorder of pregnancy associated with abnormal placentation, vascular anomalies, and systemic inflammation and hypertension. Previous research assessing inflammatory triggers of the condition used plasma, amniotic fluid, or explant samples. Studies using placental tissue from either vaginal or cesarean deliveries are confined to semiquantitative analysis using subjective scoring methods and generally involve a small sample size.
In this study, we have quantified the expression of inflammatory mediators by immunohistochemical image analysis of archived placental tissues obtained from cesarean delivery of preeclamptic, chorioamnionitic, and normal pregnancies.
Among the inflammatory mediators, we found a significant elevation in the expression of receptors of advanced glycation end products (RAGE) and two of its damage-associated molecular pattern proteins (DAMPs) and ligands, the high mobility group box protein HMGB1 and the calcium binding protein S100, in preeclamptic tissues as compared to normal placentas. In addition, we observed a significant increase in the master pro-inflammatory transcription factor, nuclear factor kappa B p65 subunit (NFκB), as well as non-significant increases in cyclooxygenase 2 (COX-2) and interleukin 8 (IL-8) in the PE group.
This study provides insight into the relationship of tissue inflammatory mediators with severe preeclampsia and the RAGE associated signaling complex, suggesting a pathogenic role for this pathway which has clinical implications for the understanding, diagnosis, and potential novel therapeutic approaches to the syndrome.
子痫前期（PE）是一种复杂的妊娠多系统疾病，与胎盘形成异常、血管异常、全身炎症和高血压有关。以往评估该疾病炎症触发因素的研究使用的是血浆、羊水或外植体样本。使用经阴道分娩或剖宫产获得的胎盘组织进行的研究仅限于使用主观评分方法的半定量分析，且样本量通常较小。
在本研究中，我们通过免疫组化图像分析对从子痫前期、绒毛膜羊膜炎和正常妊娠剖宫产获得的存档胎盘组织中炎症介质的表达进行了量化。
在炎症介质中，我们发现与正常胎盘相比，子痫前期组织中晚期糖基化终产物受体（RAGE）及其两种损伤相关分子模式蛋白（DAMPs）和配体，即高迁移率族蛋白盒1（HMGB1）和钙结合蛋白S100的表达显著升高。此外，我们观察到PE组中主要促炎转录因子核因子κB p65亚基（NFκB）显著增加，以及环氧合酶2（COX-2）和白细胞介素8（IL-8）非显著增加。
本研究深入探讨了组织炎症介质与重度子痫前期以及RAGE相关信号复合物之间的关系，表明该途径具有致病作用，这对于理解、诊断该综合征以及潜在的新治疗方法具有临床意义。
