The excessive production of inflammatory mediators by vascular endothelial cells (ECs) greatly contributes to the development of atherosclerosis. In this study, we explored the potential effect of lncRNA MALAT1 on endothelial inflammation. First, the EC inflammation model was constructed by treating human umbilical vein ECs (HUVECs) and human coronary artery ECs (HCAECs) with oxidized low-density lipoprotein (ox-LDL), which confirmed the role of MALAT1 in the inflammatory activity. Then MALAT1 was overexpressed in HUVECs and HCAECs, and the levels of inflammatory mediators and nitric oxide (NO) were examined by Western blotting, ELISA, and NO detection assay. The migration ability was confirmed by wound healing assay. The interactions among MALAT1, miR-590, and STAT3 were predicted by bioinformatics analysis and verified by qRT-PCR, Western blotting, or dual-luciferase reporter assay. MALAT1 was upregulated in ECs treated with ox-LDL, and knockdown of MALAT1 significantly inhibited ox-LDL-induced inflammation. MALAT1 overexpression potentiated the inflammatory activities of ECs, including enhanced production of inflammatory cytokines (IL-6, IL-8, and TNF-α) and adhesion molecules (VCAM1 and ICAM1), and decreased NO level and cell migratory ability. Mechanistically, MALAT1 could directly downregulate miR-590, and miR-590 could bind to the 3′-UTR of STAT3 to repress its expression. Additionally, overexpression of MALAT1-mediated inflammation was largely abrogated by the concomitant overexpression of miR-590. miR-590 knockdown activated the inflammatory response, which was reversed by STAT3 inhibition. Thus, MALAT1 serves as a proinflammatory lncRNA in ECs through regulating the miR-590/STAT3 axis, suggesting that MALAT1 may be a promising therapeutic target during the treatment of atherosclerosis.

中文翻译：

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LncRNA MALAT1 通过抵消 miR-590 的功能促进 STAT3 介导的内皮炎症

血管内皮细胞（ECs）过度产生炎症介质极大地促进了动脉粥样硬化的发展。在这项研究中，我们探讨了 lncRNA MALAT1 对内皮炎症的潜在影响。首先，EC炎症模型是通过用氧化低密度脂蛋白（ox-LDL）处理人脐静脉ECs（HUVECs）和人冠状动脉ECs（HCAECs）来构建的，这证实了MALAT1在炎症活动中的作用。然后 MALAT1 在 HUVECs 和 HCAECs 中过表达，并通过蛋白质印迹、ELISA 和 NO 检测法检测炎症介质和一氧化氮 (NO) 的水平。通过伤口愈合试验证实了迁移能力。通过生物信息学分析预测 MALAT1、miR-590 和 STAT3 之间的相互作用，并通过 qRT-PCR 验证，蛋白质印迹或双荧光素酶报告基因检测。MALAT1 在用 ox-LDL 处理的 ECs 中上调，并且 MALAT1 的敲低显着抑制了 ox-LDL 诱导的炎症。MALAT1 过表达增强了 ECs 的炎症活动，包括增强炎症细胞因子（IL-6、IL-8 和 TNF-α）和粘附分子（VCAM1 和 ICAM1）的产生，并降低 NO 水平和细胞迁移能力。从机制上讲，MALAT1 可以直接下调 miR-590，而 miR-590 可以与 STAT3 的 3'-UTR 结合以抑制其表达。此外，伴随着 miR-590 的过度表达，MALAT1 介导的炎症的过度表达在很大程度上被消除。miR-590 敲低激活了炎症反应，这被 STAT3 抑制逆转。因此，