HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function)

Atherosclerosis. 2007 Feb;190(2):321-9. doi: 10.1016/j.atherosclerosis.2006.03.037. Epub 2006 May 5.


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.

MeSH terms

  • Aorta
  • Blotting, Northern
  • Cardiovascular Diseases / therapy
  • DNA Primers
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology*
  • DNA-Binding Proteins / therapeutic use
  • Endothelin-1 / physiology
  • Endothelium, Vascular / physiology*
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / physiology
  • Heme Oxygenase-1 / genetics
  • Humans
  • Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*
  • Transcription Factors / therapeutic use


  • DNA Primers
  • DNA-Binding Proteins
  • Endothelin-1
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Transcription Factors
  • Heme Oxygenase-1