title: Simvastatin induces heat shock factor 1 in vascular endothelial cells.
abstract: 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.
authors.affiliation: Department of Medicine and Biological Science, Gunma University Course of Medical Science, Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Atsuta
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Utsugi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ohyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakata
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
authors.forename: Shoichi
authors.initials: S
authors.lastname: Tomono
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawazu
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurarbayashi
mesh_terms: 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*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D019821:Simvastatin; D008156:Luciferases; D051547:Heme Oxygenase-1