Morikawa Shigeru, Takabe Wakako, Mataki Chikage, Kanke Toru, Itoh Takahiro, Wada Youichiro, Izumi Akashi, Saito Yasushi, Hamakubo Takao, Kodama Tatsuhiko
Department of Molecular Biology, Research Center for Advanced Science and Technology, University of Tokyo, Meguro, Tokyo, Japan.
J Atheroscler Thromb. 2002;9(4):178-83. doi: 10.5551/jat.9.178.
Large-scale clinical trials have demonstrated significant reductions in cardiovascular events following statin therapy. The observed benefit of statin therapy, however, may be greater in these trials than is to be expected from lowering lipid levels alone. In order to clarify the mechanism by which statins prevent cardiovascular events in vascular wall cells, we investigated the changes in gene expression profiles after incubation with atorvastatin or pitavastatin in cultured human umbilical vein endothelial cells using DNA microarrays. Statins affected the expression levels of genes involved in inflammation, coagulation, and vascular constriction. The mRNA levels for interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) decreased after statin treatment. Statins reduced mRNA levels of plasminogen activator inhibitor-1 (PAI-1) and increased the mRNA levels of thrombomodulin. Statins reduced the mRNA levels of endothelin-1 and increased the mRNA levels of nitric oxide synthase-3 (eNOS). These results show that, statins are clinically effective because of their ability to change the gene expression profile of endothelial cells thereby preventing vascular events.
大规模临床试验表明，他汀类药物治疗后心血管事件显著减少。然而，在这些试验中观察到的他汀类药物治疗益处可能比仅通过降低血脂水平所预期的更大。为了阐明他汀类药物在血管壁细胞中预防心血管事件的机制，我们使用DNA微阵列研究了在培养的人脐静脉内皮细胞中用阿托伐他汀或匹伐他汀孵育后基因表达谱的变化。他汀类药物影响参与炎症、凝血和血管收缩的基因表达水平。他汀类药物治疗后，白细胞介素-8（IL-8）和单核细胞趋化蛋白-1（MCP-1）的mRNA水平降低。他汀类药物降低纤溶酶原激活物抑制剂-1（PAI-1）的mRNA水平，并增加血栓调节蛋白的mRNA水平。他汀类药物降低内皮素-1的mRNA水平，并增加一氧化氮合酶-3（eNOS）的mRNA水平。这些结果表明，他汀类药物具有临床疗效是因为它们能够改变内皮细胞的基因表达谱，从而预防血管事件。
