Antiaging effects of simvastatin on vascular endothelial cells

Clin Appl Thromb Hemost. 2014 Mar;20(2):212-8. doi: 10.1177/1076029612458967. Epub 2012 Sep 9.

Abstract

The anti-inflammatory, antioxidative, and antiarteriosclerosis activities of simvastatin along with its protective effects on the endothelium suggest that it may also have antiaging effects. The aim of this study was to investigate the antiaging effects of simvastatin as well as its effects on sirtuin 1 (SIRT1) expression in endothelial cells. Aged rats and human umbilical vein endothelial cells were treated with simvastatin in the presence and absence of oxidized low-density lipoprotein (OX-LDL). Aortic β-galactosidase staining was undertaken to determine senescence, and SIRT1 protein expression was evaluated using Western blot analysis. After simvastatin therapy, arterial endothelial cell aging was significantly reduced, and SIRT1 expression was significantly increased. The OX-LDL significantly accelerated the senescence of umbilical vein endothelial cells and decreased SIRT1 expression. The OX-LDL-induced downregulation of SIRT1 was blocked by simvastatin. Simvastatin treatment also reduced umbilical vein endothelial cell aging and increased SIRT1 expression.

Keywords: OX-LDL; SIRT1; antiaging; simvastatin; vascular endothelial cells.

MeSH terms

  • Aged, 80 and over
  • Animals
  • Cellular Senescence / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lipoproteins, LDL / metabolism
  • Male
  • Random Allocation
  • Rats
  • Simvastatin / pharmacology*
  • Sirtuin 1 / biosynthesis

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Simvastatin
  • SIRT1 protein, human
  • Sirt1 protein, rat
  • Sirtuin 1