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: Tsuyoshi Uchiyama, Hiroyuki Atsuta, Toshihiro Utsugi, Yoshio Ohyama, Tetsuya Nakamura, Akira Nakai, Masanori Nakata, Ikuro Maruyama, Hideaki Tomura, Fumikazu Okajima, Shoichi Tomono, Shoji Kawazu, Ryozo Nagai, Masahiko Kurarbayashi
• Journal: Atherosclerosis (Atherosclerosis) Vol. 188 Issue 2 Pg. 265-73 (Oct 2006) ISSN: 0021-9150 [Print] Ireland
• PMID: 16375908 (Publication Type: Comparative Study, Journal Article)

Chemical References

• DNA Primers
• DNA-Binding Proteins
• Heat Shock Transcription Factors
• Transcription Factors
• Simvastatin
• Luciferases
• Heme Oxygenase-1

Topics

• Analysis of Variance
• Blotting, Northern
• Blotting, Western
• DNA Primers
• DNA-Binding Proteins (metabolism)
• Endothelial Cells (metabolism)
• Gene Expression Regulation (drug effects)
• Heat Shock Transcription Factors
• Heme Oxygenase-1 (metabolism)
• Humans
• Immunohistochemistry
• Luciferases
• Plasmids (genetics)
• Protein Transport (drug effects)
• Simvastatin (pharmacology)
• Transcription Factors (metabolism)