Nutrition and proinflammatory mechanisms of PCB toxicity in the vascular endothelium

Bernhard Hennig, Michal Toborek, Larry W. Robertson

Research output: Contribution to journalArticle

Abstract

Endothelial cell dysfunction is a critical event in the initiation and acceleration of atherosclerotic lesion formation. There is evidence that exposure to certain aromatic hydrocarbons, such as polychlorinated biphenyls (PCBs), can be implicated in the development of cardiovascular diseases, such as atherosclerosis. Our data support the hypothesis that the atherogenic potential of these aromatic hydrocarbons is at the level of the vascular endothelium. However, little is known about the mechanisms underlying PCB-mediated endothelial cell dysfunction. Our data suggest that an increase in cellular oxidative stress and an imbalance in antioxidant status are critical events in PCB-mediated endothelial cell dysfunction. Furthermore, PCBs, which are ligands for the aryl hydrocarbon receptor (AhR), i.e., the more coplanar PCBs, have proinflammatory properties by inducing redox-sensitive genes critical in the inflammatory process of atherosclerosis. We also have demonstrated that specific dietary fats (unsaturated fatty acids) can further increase endothelial dysfunction induced by selected PCBs, probably by contributing to oxidative stress and the production of toxic lipid metabolites. A subsequent imbalance in cellular oxidative stress/antioxidant status can activate oxidative stress- or redox-sensitive transcription factors, which in turn can promote gene expression for inflammatory cytokines and adhesion molecules, and thus intensify a PCB-mediated inflammatory response and endothelial cell dysfunction. Our data also suggest that antioxidant nutrients (such as vitamin E) can protect against PCB-induced cell damage by interfering with signaling pathways of necrotic and apoptotic endothelial cell death. We propose that nutrition and, in particular, dietary fat and antioxidant nutrients can modify the atherogenic potential as well as cytotoxicity of PCBs.

Original languageEnglish (US)
Pages (from-to)240-244
Number of pages5
JournalFresenius Environmental Bulletin
Volume12
Issue number2
StatePublished - Jun 11 2003

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Keywords

  • Antioxidants
  • Atherosclerosis
  • Endothelial cells
  • Fatty acids
  • Nutrition
  • Oxidative stress
  • Polychlorinated biphenyls

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry

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