Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.
Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.
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DOI：
10.1152/ajpheart.01095.2008
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
Zuobiao Yuan;T. Miyoshi;Y. Bao;J. Sheehan;A. Matsumoto;Weibin Shi
中科院分区：
文献类型：
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作者：
Zuobiao Yuan;T. Miyoshi;Y. Bao;J. Sheehan;A. Matsumoto;Weibin Shi
当载脂蛋白 E (apoE(-/-)) 缺陷时，近交系小鼠 C57BL/6J (B6) 和 C3H/HeJ (C3H) 在动脉粥样硬化病变形成方面表现出显着差异，动脉壁已被确定为动脉粥样硬化易感性差异的根源。在本研究中，通过微阵列分析了两种菌株主动脉壁基因表达的差异。从喂食食物或西方饮食的 6 周龄雌性 B6 和 C3H apoE(-/-) 小鼠的主动脉中提取总 RNA。食物喂养的小鼠中有 1,514 个基因，西方喂养的小鼠中有 590 个基因被发现在两种品系之间存在差异表达。差异表达基因的通路分析表明钙信号通路在调节动脉粥样硬化易感性中发挥作用。氧化低密度脂蛋白 (oxLDL) 会导致 B6 内皮细胞中胞浆钙水平呈剂量依赖性上升。钙螯合剂EGTA或细胞内钙捕获化合物BAPTA预处理可抑制oxLDL诱导的单核细胞趋化蛋白1的产生，表明钙离子介导了oxLDL对单核细胞趋化蛋白1诱导的影响。目前的研究结果表明钙信号通路参与动脉粥样硬化的炎症过程。
Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit a marked difference in atherosclerotic lesion formation when deficient in apolipoprotein E (apoE(-/-)), and the arterial wall has been identified as a source of the difference in atherosclerosis susceptibility. In the present study, differences in gene expression in aortic walls of the two strains were analyzed by microarrays. Total RNA was extracted from the aorta of 6-wk-old female B6 and C3H apoE(-/-) mice fed a chow or Western diet. There were 1,514 genes in chow fed mice and 590 genes in Western fed mice that were found to be differentially expressed between the two strains. Pathway analysis of differentially expressed genes suggested a role for the calcium signaling pathway in regulating atherosclerosis susceptibility. Oxidized LDL (oxLDL) induced a dose-dependent rise in cytosolic calcium levels in B6 endothelial cells. oxLDL-induced monocyte chemoattractant protein-1 production was inhibited by pretreatment with calcium chelator EGTA or intracellular calcium trapping compound BAPTA, indicating that calcium ions mediate the effect of oxLDL on monocyte chemoattractant protein-1 induction. The present findings demonstrate involvement of the calcium signaling pathway in the inflammatory process of atherogenesis.