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

一些证据表明，氧化修饰的低密度脂蛋白在动脉粥样硬化形成中起着关键作用。氧化低密度脂蛋白致动脉粥样硬化的机制尚不清楚。因此，我们利用DNA芯片技术研究了氧化型低密度脂蛋白刺激诱导的所有基因的表达。结果发现，氧化型低密度脂蛋白刺激后，细胞内ID3(helix-loop-helix，ID3)基因表达增强，CDK抑制因子p21WAF/Cipl和p27Kipl表达降低。经放线菌素D处理后，氧化型低密度脂蛋白诱导的血管平滑肌细胞ID3mRNA表达增强，提示氧化低密度脂蛋白诱导ID3mRNA表达的机制可能与转录增加和mRNA稳定有关。SB203580、p38MAPK抑制剂或p38MAPK表达的显性负突变可抑制ID3mRNA的表达。结论：氧化型低密度脂蛋白诱导VSMC增殖与细胞周期相关蛋白螺旋-环-螺旋ID3交叉相关，但具体机制有待进一步研究。

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.