Studies for the Mechanisms of oxidized LDL-induced growth in vascular smooth muscle cells

氧化LDL诱导血管平滑肌细胞生长机制的研究

• 批准号: 15590764
• 负责人: YAMAKAWA Tadashi
• 金额: $ 2.18万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590764/
• 关键词: Oxidized LDL; vascular smooth muscle; Id3; p38MAPK; p38 MAPK; luciferase assay

Several lines of evidence have suggested that oxidatively modified LDL plays a key role in atherogenesis. The mechanisms of atherogenesis by oxidized LDL remains unknown. Therefore, we totally investigated all expressed genes induced by the stimulation with oxidized LDL by using DNA chip analysis. It was found that helix-loop-helix Id3 (Id3) mRNA expression was enhanced and CDK-inhibitor, p21WAF/Cipl and p27Kipl expression were decreased by oxidized LDL stimulation.We constructed Id3 promotoro/luciferase chimera plasmid and then analyzed oxidized LDL-induced luciferase activity. Pretreatment of Actinomycin D, oxidized LDL induced Id3 mRNA expression was enhanced suggesting that the mechanisms of Id3 expression might be increased transcription and mRNA stability.Id3 mRNA expression was inhibited with SB203580, p38 MAPK inhibitors, or dominant negative mutant of p38MAPK expression.In conclusion, VSMC growth by oxidized LDL is crossly associated with cell cycle related protein, helix-loop-helix Id3, however, detailed mechanisms are necessary to do further investigation.

多项证据表明，氧化修饰的低密度脂蛋白在动脉粥样硬化形成中发挥着关键作用。氧化低密度脂蛋白引起动脉粥样硬化的机制仍不清楚。因此，我们通过DNA芯片分析全面研究了氧化LDL刺激诱导的所有表达基因。结果发现，氧化LDL刺激后，螺旋-环-螺旋Id3（Id3）mRNA表达增强，CDK抑制剂、p21WAF/Cipl和p27Kipl表达减少。我们构建了Id3启动子/荧光素酶嵌合质粒，然后分析了氧化LDL诱导的荧光素酶活性。放线菌素 D 预处理，氧化 LDL 诱导 Id3 mRNA 表达增强，表明 Id3 表达的机制可能是增加转录和 mRNA 稳定性。SB203580、p38 MAPK 抑制剂或 p38MAPK 表达显性失活突变体抑制 Id3 mRNA 表达。 ，氧化LDL导致的VSMC生长与细胞周期相关蛋白螺旋-环-螺旋Id3交叉相关，然而，详细机制是有必要做进一步的调查。