RNA interference for HIF-1α inhibits foam cells formation in vitro
RNA interference for HIF-1α inhibits foam cells formation in vitro
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DOI：
10.1016/j.ejphar.2007.01.066
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发表时间：
2007-05-21
影响因子：
5
通讯作者：
Lou, Yijia
中科院分区：
文献类型：
--
作者：
Jiang, Guojun;Li, Tiejun;Lou, Yijia
巨噬细胞衍生的泡沫细胞通常被认为在动脉粥样硬化病变的病理中起主要作用。缺氧诱导因子-1 α (HIF-1 α)最近被发现在动脉粥样硬化中起重要作用。本研究采用RNA干扰技术研究了HIF-1 α在泡沫细胞形成中的作用。实时RT-PCR、Western blot检测转染HIF-1 α - sirna可降低HIF-1 α的MRNA和蛋白水平。利用DNA微阵列进行大规模基因表达分析，发现用小干扰RNA （HIF-1 α - sirna）干扰HIF-1 α可抑制氧化低密度脂蛋白（ox-LDL）处理的人单母细胞系（U937）泡沫细胞的形成，而环氧化酶-2 （COX-2）、血管细胞粘附分子-1 （VCAM-1）、白细胞介素-1 β (IL-1 β)等大多数动脉粥样硬化相关基因均下调。这些数据表明，动脉粥样硬化因子诱导HIF-1 α可能是协调导致动脉粥样硬化病变的细胞事件的关键步骤。(c) 2007 Elsevier B.V.版权所有
Macrophage-derived foam cells in atherosclerotic lesions are generally thought to play a major role in the pathology of the disease. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) was recently found to play an important role in atherosclerosis. Here we applied RNA interference to study the role of HIF-1 alpha in foam cell fort-nation in vitro. Transfeclion of HIF-1 alpha-siRNA reduced HIF-1 alpha synthesis as measured on MRNA and protein level by real-time RT-PCR, Western blot. It was found that RNA interference for HIF-1 alpha with small interfering RNAs (HIF-1 alpha-siRNA) inhibits foam cell formation by the human monoblastic cell line (U937) which was treated with oxidized low-density lipoprotein (ox-LDL) while the majority of atherosclerosis-related genes, such as cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 beta (IL-1 beta), and so on, were down-regulated, through large scale gene expression analysis using DNA microarrays. These data demonstrate that induction of HIF-1 alpha by atherogenic factors may be a key step in coordinating the cellular events that result in atherosclerotic lesions. (c) 2007 Elsevier B.V. All rights reserved.