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HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function) |
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| Authors: | Uchiyama Tsuyoshi Atsuta Hiroyuki Utsugi Toshihiro Oguri Masato Hasegawa Akira Nakamura Tetsuya Nakai Akira Nakata Masanori Maruyama Ikuro Tomura Hideaki Okajima Fumikazu Tomono Shoichi Kawazu Shoji Nagai Ryozo Kurabayashi Masahiko |
| Institution: | aDepartment of Medicine and Biological Science, Gunma University Course of Medical Science Graduate School of Medicine, 3-39-15, Showa-machi Maebashi, Gunma 371-8511, Japan bClinical Investigation Unit, Gunma University Hospital, Maebashi, Gunma, Japan cDepartment of Biochemistry and Molecular Biology, Yamaguchi University of School of Medicine, Japan dDivision of Integrative Physiology, Department of Physiology, Jichi Medical School, Tochigi, Japan eLaboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan fLaboratory of Signal Transduction and Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan gSchool of Health Science, Faculty of Medicine, Gunma University, Maebashi, Gunma, Japan hSaitama Medical School Hospital, Health Management Center, Saitama, Japan iDepartment of Cardiovascular Disease, Graduate School of Medicine, University of Tokyo, Tokyo, Japan |
| Abstract: | 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. |
| Keywords: | HSF1 Heat shock protein Endothelium PAI-1 Endothelin-1 eNOS Thrombomodulin |
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