, Volume 37, Issue 1, pp 177–185 | Cite as

The Protective Effect of Fenofibrate Against TNF-α-Induced CD40 Expression through SIRT1-Mediated Deacetylation of NF-κB in Endothelial Cells

  • Weirong Wang
  • Ling Bai
  • Hu Qiao
  • Yanxiang Li
  • Lina Yang
  • Jiye Zhang
  • Rong Lin
  • Feng Ren
  • Jianfeng Zhang
  • Meixi Ji


Fenofibrate, as a lipid-lowering drug in clinic, participates in the regulation of inflammatory response. Recently, increasing studies have indicated that sirtuin1 (SIRT1), a NAD+-dependent deacetylase, has potential anti-inflammatory effect in endothelial cells. However, whether the regulatory effect of fenofibrate on inflammation response is mediated by SIRT1 remains unclear. The aim of this study was to investigate the effect of fenofibrate on the expressions of SIRT1 and pro-inflammatory cytokine CD40 in endothelial cells and explore the underlying mechanisms. The results showed that fenofibrate upregulated SIRT1 expression and inhibited CD40 expression in TNF-α-stimulated endothelial cells, but these effects were reversed by peroxisome proliferator-activated receptor-α (PPARα) antagonist GW6471. Furthermore, SIRT1 inhibitors sirtinol/nicotinamide (NAM) or SIRT1 knockdown could attenuate the effect of fenofibrate on CD40 expression in endothelial cells. Importantly, NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) augmented the effect of fenofibrate on CD40 expression. Further study found that fenofibrate decreased the expression of acetylated-NF-κB p65 (Ac-NF-κB p65) in TNF-α-stimulated endothelial cells, which was abolished by SIRT1 knockdown. These results indicate that fenofibrate has protective effect against TNF-α-induced CD40 expression through SIRT1-mediated deacetylation of the p65 subunit of NF-κB.


fenofibrate SIRT1 NF-κB CD40 endothelial cells 



This study was supported by National Natural Science Foundation of China (Nos. 81072643 and 81270347) and Natural Science Foundation of Shaanxi Province (2012JQ4025).

Conflict of Interest



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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Weirong Wang
    • 1
  • Ling Bai
    • 2
  • Hu Qiao
    • 3
  • Yanxiang Li
    • 1
  • Lina Yang
    • 1
  • Jiye Zhang
    • 1
  • Rong Lin
    • 1
  • Feng Ren
    • 1
  • Jianfeng Zhang
    • 1
  • Meixi Ji
    • 1
  1. 1.Department of Pharmacology, Cardiovascular Research Center, School of MedicineXi’an Jiaotong UniversityXi’anChina
  2. 2.The Cardiovascular Department of The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  3. 3.Department of Physiology and Pathophysiology, School of MedicineXi’an Jiaotong UniversityXi’anChina

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