HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function)
- 作者：Tsuyoshi Uchiyama ; Hiroyuki Atsuta ; Toshihiro Utsugi ; Masato Oguri ; Akira Hasegawa ; Tetsuya Nakamura ; Akira Nakai ; Masanori Nakata ; Ikuro Maruyama ; Hideaki Tomura ; et al.
- 关键词：HSF1 ; Heat shock protein ; Endothelium ; PAI-1 ; Endothelin-1 ; eNOS ; Thrombomodulin
- 刊名：Atherosclerosis
- 出版年：2007
- 期刊代码：28_00219150
- 类别：med
- 出版时间：February 2007
- 卷：190
- 期：2
- 页码：321-329
- 文件大小：798 K
摘要
We have been examining the role of heat shock factor 1 (HSF1) in the pleiotropic effects of statins. In parallel studies, we found that statin induces the nuclear translocation of HSF1 and that a decoy oligonucleotide encoding the heat shock element inhibits the statin-induced expression of heat shock protein 70, endothelial nitric oxide synthase (eNOS) and thrombomodulin. Also, in vascular endothelial cells, increases in the expression of human HSF1 corresponded with elevated steady-state levels of eNOS and thrombomodulin and reduced levels of endothelin-1 and plasminogen activator inhibitor-1. We also found that heat shock proteins induced eNOS and thrombomodulin expression and reduced PAI-1 and ET-1 expression. In particular, a combination of HSP70 and HSP90 strongly induced eNOS expression and reduced PAI-1 expression. In the current studies, we generated a constitutively active form of HSF1 and found that it is more effective than the wild-type HSF at inducing thrombomodulin and eNOS expression and decreasing endothelin-1 and plasminogen activator inhibitor-1 expression. These results show that the wild-type and constitutively active forms of HSF1 induce anticoagulation and relaxation factors in vascular endothelial cells and could therefore be used to treat cardiovascular disease.