Preeclampsia and Gestational Hypertension: Biochemical and Antioxidant Features in Vitro Might Help Understand Different Outcomes

Abstract Objective Gestational hypertension (GH) is characterized by increased blood pressure after the 20th gestational week; the presence of proteinuria and/or signs of end-organ damage indicate preeclampsia (PE). Heme oxygenase-1 (HO-1) is an antioxidant enzyme with an important role in maintaining endothelial function, and induction of HO-1 by certain molecules shows potential in attenuating the condition’s effects over endothelial tissue. HO-1 production can also be stimulated by potassium iodide (KI). Therefore, we evaluated the effects of KI over HO-1 expression in human umbilical vein endothelial cells (HUVECs) incubated with plasma from women diagnosed with GH or PE. Methods Human umbilical vein endothelial cells were incubated with a pool of plasma of healthy pregnant women (n = 12), pregnant women diagnosed with GH (n = 10) or preeclamptic women (n = 11)with or without the addition of KI for 24 hours to evaluate its effect on this enzyme expression. Analysis of variance was performed followed by Dunnet’s test for multiple comparisons between groups only or between groups with addition of KI (p ≤ 0.05). Results KI solution (1,000 µM) reduced HO-1 in the gestational hypertension group (p = 0.0018) and cytotoxicity in the preeclamptic group (p = 0.0143); treatment with KI reduced plasma cytotoxicity but did not affect the preeclamptic group’s HO-1 expression. Conclusion Our findings suggest that KI alleviates oxidative stress leading to decreased HO-1 expression; plasma from preeclamptic women did not induce the enzyme’s expression in HUVECs, and we hypothesize that this is possibly due to inhibitory post-transcriptional mechanisms in response to overexpression of this enzyme during early pregnancy.

摘要：研究背景 妊娠高血压（Gestational hypertension, GH）以妊娠20周后血压升高为典型特征；若同时存在蛋白尿和/或终末器官损伤体征，则可诊断为子痫前期（preeclampsia, PE）。血红素氧合酶-1（Heme oxygenase-1, HO-1）是一类抗氧化酶，在维持内皮细胞功能过程中发挥关键作用，部分小分子诱导HO-1表达可有效减轻其对内皮组织的损伤。碘化钾（potassium iodide, KI）同样可刺激HO-1的生成。因此，本研究旨在评估碘化钾对经妊娠高血压或子痫前期女性血浆孵育的人脐静脉内皮细胞（human umbilical vein endothelial cells, HUVECs）中HO-1表达的影响。方法：将人脐静脉内皮细胞分别与健康孕妇（n=12）、妊娠高血压患者（n=10）或子痫前期患者（n=11）的混合血浆孵育，同时添加或不添加碘化钾，孵育时长为24小时，以检测其对该酶表达的调控作用。采用方差分析进行统计检验，随后针对单纯组间或添加碘化钾后的组间多重比较，采用Dunnet检验进行后续分析（p≤0.05）。结果：1000 μM碘化钾可显著降低妊娠高血压组的HO-1表达水平（p=0.0018），并减轻子痫前期组的细胞毒性（p=0.0143）；碘化钾处理可降低血浆诱导的细胞毒性，但未对子痫前期组的HO-1表达产生显著影响。结论：本研究结果提示，碘化钾可通过减轻氧化应激进而下调HO-1的表达；子痫前期女性的血浆无法诱导人脐静脉内皮细胞中该酶的表达，我们推测这一现象可能与妊娠早期该酶过表达时所触发的转录后抑制机制相关。