Simvastatin induces heat shock factor 1 in vascular endothelial cells
Simvastatin induces heat shock factor 1 in vascular endothelial cells
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DOI：
10.1016/j.atherosclerosis.2005.10.045
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发表时间：
2006-10-01
期刊：
影响因子：
5.3
通讯作者：
Kurarbayashi, Masahiko
中科院分区：
文献类型：
--
作者：
Uchiyama, Tsuyoshi;Atsuta, Hiroyuki;Kurarbayashi, Masahiko
他汀类药物不仅可以降低血清胆固醇，还可以改善血管内皮功能，这与其降脂作用无关。然而，除了他汀类药物诱导一氧化氮的机制外，他汀类药物多效性的生理基础尚不清楚。在本研究中，我们研究了他汀类药物对血管内皮细胞功能的影响与热休克蛋白的关系。我们发现，在血管内皮细胞中，辛伐他汀增加了热休克蛋白90和70以及血红素加氧酶-1的稳态水平，并导致热休克因子1的核转位。编码热休克元件的诱骗寡核苷酸抑制了他汀类药物诱导的节拍休克蛋白70、内皮型一氧化氮合酶和血栓调节蛋白的表达。该诱骗寡核苷酸还抑制他汀类药物降低内皮素-1和纤溶酶原激活物抑制物-1表达的能力。这些结果表明，他汀类药物通过热休克因子1改善血管内皮功能，这可能与其改善心血管疾病的能力有关。(C)2005爱思唯尔爱尔兰有限公司。保留所有权利。
Statins not only reduce serum cholesterol but they also improve vascular endothelial function independent of their lipid-lowering effects. However, except for the mechanism of nitric oxide induction via calveolin, the physiologic basis for the pleiotropic effect of statins remains unknown. In the present study, we investigated the relationship between the effects of statins on vascular endothelial cell function and heat shock proteins. We found that, in vascular endothelial cells, simvastatin increased the steady-state levels of heat shock proteins 90 and 70, and heme oxygenase-1 and caused the nuclear translocation of heat shock factor 1. A decoy oligonucleotide encoding the heat shock element inhibited statin-induced expression of beat shock protein 70, endothelial nitric oxide synthase, and thrombomodulin. This decoy oligonucleotide also inhibited the ability of statin to reduce endothelin-1 and plasminogen activator inhibitor-1 expression. These results indicate that statins improve vascular endothelial function via heat shock factor 1, which may contribute to their ability to improve cardiovascular disease. (c) 2005 Elsevier Ireland Ltd. All rights reserved.