Table_1_The Role of Iron in Atherosclerosis in Apolipoprotein E Deficient Mice.pdf

The role of iron in atherosclerosis is still a controversial and unsolved issue. Here, we investigated serum iron, expression of iron regulatory, transport and storage proteins, pro-inflammatory chemokines and cytokines in ApoE–/– mice. We demonstrated that ApoE–/– induced atherosclerosis and an increase in iron contents, expression of transferrin receptor 1 (TfR1), iron regulatory proteins (IRPs), heme oxygenase 1 (HO1), cellular adhesion molecules and pro-inflammatory cytokines, production of reactive oxygen species (ROS), and a reduction in expression of superoxide dismutase and glutathione peroxidase enzyme in aortic tissues. All of these changes induced by ApoE deficiency could be significantly abolished by deferoxamine. The data showed that the increased iron in aortic tissues was mainly due to the increased iron uptake via IRP/TfR1 upregulation. These findings plus a brief analysis of the controversial results reported previously showed that ApoE deficiency-induced atherosclerosis is partly mediated by the increased iron in aortic tissues.

铁在动脉粥样硬化（atherosclerosis）中的作用至今仍存在争议且尚未明确解决。本研究以载脂蛋白E基因敲除（ApoE–/–）小鼠为模型，检测了其血清铁水平、铁调节、转运与储存蛋白的表达情况，以及促炎趋化因子与细胞因子的表达水平。研究结果显示，ApoE–/–可诱导动脉粥样硬化发生，并使小鼠主动脉组织内铁含量升高，转铁蛋白受体1（TfR1）、铁调节蛋白（IRPs）、血红素加氧酶1（HO1）、细胞黏附分子与促炎细胞因子的表达上调，活性氧（ROS）生成增加，同时超氧化物歧化酶（superoxide dismutase）与谷胱甘肽过氧化物酶（glutathione peroxidase）的表达水平显著降低。去铁胺（deferoxamine）可显著逆转ApoE基因缺失诱导的上述全部异常变化。数据分析表明，主动脉组织内铁含量升高主要源于IRP/TfR1通路上调所介导的铁摄取增加。结合本研究发现与对既往报道的争议性研究结果的简要分析，我们认为ApoE基因缺失诱导的动脉粥样硬化，部分由主动脉组织内铁含量升高所介导。