文亮, 李洁, 张敏霞, 薛强. MIF介导ox-LDL对内皮细胞功能的影响及作用机制[J]. 心脏杂志, 2023, 35(6): 629-636. DOI: 10.12125/j.chj.202208094
    引用本文: 文亮, 李洁, 张敏霞, 薛强. MIF介导ox-LDL对内皮细胞功能的影响及作用机制[J]. 心脏杂志, 2023, 35(6): 629-636. DOI: 10.12125/j.chj.202208094
    WEN Liang, LI Jie, ZHANG Min-xia, XUE Qiang. Macrophage migration inhibitory factor mediated effect of oxidized low density lipoprotein on endothelial cell function and its mechanism[J]. Chinese Heart Journal, 2023, 35(6): 629-636. DOI: 10.12125/j.chj.202208094
    Citation: WEN Liang, LI Jie, ZHANG Min-xia, XUE Qiang. Macrophage migration inhibitory factor mediated effect of oxidized low density lipoprotein on endothelial cell function and its mechanism[J]. Chinese Heart Journal, 2023, 35(6): 629-636. DOI: 10.12125/j.chj.202208094

    MIF介导ox-LDL对内皮细胞功能的影响及作用机制

    Macrophage migration inhibitory factor mediated effect of oxidized low density lipoprotein on endothelial cell function and its mechanism

    • 摘要:
      目的  探讨巨噬细胞迁移抑制因子(MIF)介导氧化型低密度脂蛋白(ox-LDL)对血管内皮细胞功能的影响及其作用机制。
      方法  人脐静脉内皮细胞(HUVECS),给予ox-LDL(100 nmol/L)处理,蛋白免疫电泳检测相关蛋白的表达及功能;实时定量PCR监测炎症相关因子的表达;药物阻断和基因干预关键分子观察对下游基因的表达的影响;Griess反应检测在干预措施下内皮细胞一氧化氮(NO)的产生情况;体外用乙酰胆碱诱导的血管舒张反应作为评估内皮依赖性血管舒张功能的指标检测内皮细胞功能。
      结果  ox-LDL能增加内皮细胞胆固醇调节元件结合蛋白(SREBP2)和MIF的表达,应用药物特异性阻断以及siRNA 抑制MIF的表达均可显著降低SREBP2的表达和激活(P<0.05);离体实验证实MIF通过SREBP2抑制血管内皮细胞功能(P<0.05)。
      结论  ox-LDL等氧化应激刺激能通过MIF增加SREBP2介导的炎症小体(inflammasome)的表达和炎症相关内皮细胞表面黏附分子的表达,从而破坏内皮细胞功能,这可能是动脉粥样硬化(AS)发生发展的重要机制之一。

       

      Abstract:
      AIM To investigate macrophage migration inhibitory factor (MIF) mediated effect of oxidized low density lipoprotein (ox-LDL) on vascular endothelial cell function and its mechanism.
      METHODS Human umbilical vein endothelial cells (HUVECS) were treated with ox-LDL (100 nmol/L) and the expression and function of related proteins were detected by immunoelectrophoresis. Real-time quantitative PCR was used to monitor the expression of inflammatory factors and the effects of drug blockade and gene intervention on the expression of downstream genes were observed. Griess response was used to monitor NO production in endothelial cells under the intervention. Ex vivo, acetylcholine-induced vasodilation was used as an indicator of endothelium-dependent vasodilation to detect endothelial cell function.
      RESULTS ox-LDL increased the expression of sterol regulatory element binding protein (SREBP2) and MIF, and either drug specific blockage or siRNA inhibition of MIF expression significantly reduced the expression and activation of SREBP2 (P<0.05). MIF regulated vascular endothelial cell function through SREBP2 (P<0.05).
      CONSCLUSIONS  Oxidative stress such as ox-LDL can increase the expression of SREBP2-mediated inflammasome and inflamma-related adhesion molecules on endothelial cells through MIF, thereby disrupting endothelial cell function, which is one of the important mechanisms for the occurrence and development of atherosclerosis.

       

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