SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis

Eur Heart J. 2010 Sep;31(18):2301-9. doi: 10.1093/eurheartj/ehq107. Epub 2010 Apr 23.


Aims: Endothelial activation, macrophage infiltration, and foam cell formation are pivotal steps in atherogenesis. Our aim in this study was to analyse the role of SIRT1, a class III deacetylase with important metabolic functions, in plaque macrophages and atherogenesis.

Methods and results: Using partial SIRT1 deletion in atherosclerotic mice, we demonstrate that SIRT1 protects against atherosclerosis by reducing macrophage foam cell formation. Peritoneal macrophages from heterozygous SIRT1 mice accumulate more oxidized low-density lipoprotein (oxLDL), thereby promoting foam cell formation. Bone marrow-restricted SIRT1 deletion confirmed that SIRT1 function in macrophages is sufficient to decrease atherogenesis. Moreover, we show that SIRT1 reduces the uptake of oxLDL by diminishing the expression of lectin-like oxLDL receptor-1 (Lox-1) via suppression of the NF-κB signalling pathway.

Conclusion: Our findings demonstrate protective effects of SIRT1 in atherogenesis and suggest pharmacological SIRT1 activation as a novel anti-atherosclerotic strategy by reducing macrophage foam cell formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / etiology*
  • Atherosclerosis / prevention & control
  • Bone Marrow Transplantation
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cholesterol / metabolism
  • Foam Cells / pathology*
  • Gene Deletion
  • Hypercholesterolemia / metabolism
  • Hypercholesterolemia / pathology
  • Lipoproteins / metabolism
  • Lipoproteins, LDL / metabolism
  • Macrophages, Peritoneal / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Scavenger Receptors, Class E / physiology*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / physiology*


  • Lipoproteins
  • Lipoproteins, LDL
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • Cholesterol
  • SIRT1 protein, human
  • Sirtuin 1