SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

Sci China Life Sci. 2013 Jan;56(1):19-25. doi: 10.1007/s11427-012-4407-7. Epub 2012 Dec 12.


Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin (PMA/Io) in human umbilical vein endothelial cells (HUVECs). Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression in HUVECs. Knockdown of SIRT1 by RNA interference (RNAi) resulted in increased expression of ICAM-1 in HUVECs. Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation (ChIP) assays. Furthermore, SIRT1 RNAi increased NF-κB p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Gene Expression / genetics
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Ionomycin / pharmacology*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology*


  • Intercellular Adhesion Molecule-1
  • Ionomycin
  • Luciferases
  • SIRT1 protein, human
  • Sirtuin 1
  • Tetradecanoylphorbol Acetate