HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function).
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.
Uchiyama
Tsuyoshi
T
Department of Medicine and Biological Science, Gunma University Course of Medical Science Graduate School of Medicine, 3-39-15, Showa-Machi Maebashi, Gunma, Japan. uchiyat@med.gunma-u.ac.jp
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Utsugi
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Hasegawa
Akira
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Nakamura
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Nakai
Akira
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Nakata
Masanori
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Maruyama
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Tomura
Hideaki
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Okajima
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Tomono
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Kawazu
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Nagai
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Kurabayashi
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