PPARα ligands reduce PCB-induced endothelial activation: Possible interactions in inflammation and atherosclerosis

Xabier Arzuaga, Gudrun Reiterer, Zuzana Majkova, Michael W. Kilgore, Michal J Toborek, Bernhard Hennig

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 proinflammatory effects could be mediated, in part, by inhibition of PPARα expression and function.

Original languageEnglish
Pages (from-to)264-272
Number of pages9
JournalCardiovascular Toxicology
Volume7
Issue number4
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Polychlorinated Biphenyls
Atherosclerosis
Chemical activation
Ligands
Inflammation
Endothelial cells
Endothelial Cells
Aryl Hydrocarbon Receptors
Fenofibrate
Proteins
Vascular Cell Adhesion Molecule-1
MCF-7 Cells
Reporter Genes
Gene expression
Cytochrome P-450 Enzyme System
Nutrients
Down-Regulation
Genes

Keywords

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

ASJC Scopus subject areas

  • Toxicology
  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

Cite this

PPARα ligands reduce PCB-induced endothelial activation : Possible interactions in inflammation and atherosclerosis. / Arzuaga, Xabier; Reiterer, Gudrun; Majkova, Zuzana; Kilgore, Michael W.; Toborek, Michal J; Hennig, Bernhard.

In: Cardiovascular Toxicology, Vol. 7, No. 4, 01.12.2007, p. 264-272.

Research output: Contribution to journalArticle

Arzuaga, Xabier ; Reiterer, Gudrun ; Majkova, Zuzana ; Kilgore, Michael W. ; Toborek, Michal J ; Hennig, Bernhard. / PPARα ligands reduce PCB-induced endothelial activation : Possible interactions in inflammation and atherosclerosis. In: Cardiovascular Toxicology. 2007 ; Vol. 7, No. 4. pp. 264-272.
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