Department of Immunobiochemistry, Instituto Nacional de Perinatología, Mexico City 11000, Mexico.
Postgraduate in Experimental Biology, Division of Biological and Health Sciences, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09310, Mexico.
Int J Mol Sci. 2023 Dec 21;25(1):122. doi: 10.3390/ijms25010122.
Endothelial dysfunction (ED) in preeclampsia (PE) results from the convergence of oxidative stress, inflammation, and alterations in extracellular matrix components, affecting vascular tone and permeability. The molecular network leading to ED includes IL-8 and MMP-2. In vitro, IL-8 regulates the concentration and activity of MMP-2 in the trophoblast; this interaction has not been studied in endothelial cells during PE. We isolated human umbilical vein endothelial cells (HUVECs) from women with healthy pregnancies (NP, = 15) and PE ( = 15). We quantified the intracellular concentration of nitric oxide and reactive oxygen species with colorimetric assays, IL-8 with ELISA, and MMP-2 with zymography and using an ELISA-type system. An IL-8 inhibition assay was used to study the influence of this cytokine on MMP-2 concentration and activity. HUVECs from women with PE showed significantly higher oxidative stress than NP. IL-8 and MMP-2 were found to be significantly elevated in PE HUVECs compared to NP. Inhibition of IL-8 in HUVECs from women with PE significantly decreased the concentration of MMP-2. We demonstrate that IL-8 is involved in the mechanisms of MMP-2 expression in HUVECs from women with PE. Our findings provide new insights into the molecular mechanisms regulating the ED distinctive of PE.
子痫前期（PE）中的内皮功能障碍（ED）源于氧化应激、炎症和细胞外基质成分改变的汇聚，影响血管张力和通透性。导致 ED 的分子网络包括白细胞介素 8（IL-8）和基质金属蛋白酶 2（MMP-2）。在体外，IL-8 调节滋养层中 MMP-2 的浓度和活性；在 PE 期间，内皮细胞中尚未研究这种相互作用。我们从健康妊娠（NP）妇女（n = 15）和 PE 妇女（n = 15）中分离出人脐静脉内皮细胞（HUVEC）。我们使用比色法测定细胞内一氧化氮和活性氧的浓度，ELISA 测定 IL-8，明胶酶谱法和 ELISA 型系统测定 MMP-2。进行 IL-8 抑制测定以研究该细胞因子对 MMP-2 浓度和活性的影响。PE 妇女的 HUVEC 显示出明显更高的氧化应激。与 NP 相比，PE HUVEC 中的 IL-8 和 MMP-2 明显升高。PE 妇女的 HUVEC 中 IL-8 的抑制显著降低了 MMP-2 的浓度。我们证明 IL-8 参与了 PE 妇女的 HUVEC 中 MMP-2 表达的机制。我们的研究结果为调节 PE 特征性 ED 的分子机制提供了新的见解。
