Simvastatin induces heat shock factor 1 in vascular endothelial cells.
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 heat 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.
Uchiyama
Tsuyoshi
T
Department of Medicine and Biological Science, Gunma University Course of Medical Science, Graduate School of Medicine, Maebashi, Gunma, Japan.
Atsuta
Hiroyuki
H
Utsugi
Toshihiro
T
Ohyama
Yoshio
Y
Nakamura
Tetsuya
T
Nakai
Akira
A
Nakata
Masanori
M
Maruyama
Ikuro
I
Tomura
Hideaki
H
Okajima
Fumikazu
F
Tomono
Shoichi
S
Kawazu
Shoji
S
Nagai
Ryozo
R
Kurarbayashi
Masahiko
M
D000704:Analysis of Variance; D015152:Blotting, Northern; D015153:Blotting, Western; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D000076249:Heat Shock Transcription Factors; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D010957:Plasmids / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D019821:Simvastatin; D008156:Luciferases; D051547:Heme Oxygenase-1