Cardiovascular Toxicology

, Volume 7, Issue 4, pp 264–272 | Cite as

PPARα Ligands Reduce PCB-Induced Endothelial Activation: Possible Interactions in Inflammation and Atherosclerosis

  • Xabier Arzuaga
  • Gudrun Reiterer
  • Zuzana Majkova
  • Michael W. Kilgore
  • Michal Toborek
  • Bernhard HennigEmail author


Exposure to polychlorinated biphenyls (PCBs) can activate inflammatory responses in vascular endothelial cells. Activation of peroxisome proliferator-activated receptors (PPARs) by nutrients or synthetic agonists has been shown to block pro-inflammatory responses both in vitro and in vivo. Here we demonstrate that activation of PPARα by synthetic agonists can reduce 3,3′4,4′-tetrachlorobiphenyl (PCB77)-induced endothelial cell activation. Primary vascular endothelial cells were pretreated with the PPARα ligands fenofibrate or WY14643 followed by exposure to PCB77. PPARα activation protected endothelial cells against PCB77-induced expression of the pro-inflammatory proteins vascular cell adhesion molecule-1 (VCAM-1), cycloxygenase-2 (COX-2), and PCB77-induced expression and activity of the aryl hydrocarbon receptor (AHR) responsive cytochrome P450 1A1 (CYP1A1). Furthermore, basal AHR expression was downregulated by fenofibrate and WY14643. We also investigated the possible interactions between PCBs, and basal PPAR activity and protein expression. Treatment with PCB77 significantly reduced basal mRNA expression of PPARα and the PPAR responsive gene CYP4A1, as well as PPARα protein expression. Also, PCB77 exposure caused a significant decrease in basal PPAR-dependent reporter gene expression in MCF-7 cells. Overall, these findings suggest that PPARα agonists can reduce PCB77 induction of endothelial cell activation by inhibition of the AHR pathway, and that coplanar PCB induced pro-inflammatory effects could be mediated, in part, by inhibition of PPARα expression and function.


Atherosclerosis Vascular endothelial cells PPARα PPARγ PCB AHR CYP1A1 VCAM-1 COX-2 Inflammation 



This study was supported in part by grants from NIEHS/NIH (ES 07380), the KY AES, and the University of Kentucky Lyman T. Johnson Postdoctoral Fellowship. G. Reiterer is a recipient of the American Heart Association predoctoral fellowship.


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Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Xabier Arzuaga
    • 1
  • Gudrun Reiterer
    • 1
    • 2
  • Zuzana Majkova
    • 1
  • Michael W. Kilgore
    • 3
  • Michal Toborek
    • 2
    • 4
  • Bernhard Hennig
    • 1
    • 2
    Email author
  1. 1.Molecular and Cell Nutrition Laboratory, College of AgricultureUniversity of KentuckyLexingtonUSA
  2. 2.Graduate Center for Nutritional SciencesUniversity of KentuckyLexingtonUSA
  3. 3.Department of PharmacologyUniversity of KentuckyLexingtonUSA
  4. 4.Department of NeurosurgeryUniversity of KentuckyLexingtonUSA

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