Linoleic acid and TNF-α cross-amplify oxidative injury and dysfunction of endothelial cells

Michal Toborek, Steven W. Barger, Mark P. Mattson, Shirish Barve, Craig J. McClain, Bernhard Hennig

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Factors implicated in the development of atherosclerosis include metabolic alterations of the endothelium induced by certain lipids and inflammatory cytokines. To study the hypothesis that the combined presence of unsaturated fatty acids and inflammatory cytokines may cross-amplify their individual injurious effects, cultured endothelial cells were treated with 90 μM of linoleic acid (18:2 n-6) and/or 20 ng/ml (100 U/ml) of tumor necrosis factor- α (TNF) for up to 24 h. Disturbances in endothelial cell metabolism were determined by measuring cellular oxidative stress, oxidative stress-inducible nuclear factor-κB (NF-κB) and NF-κB-related transcription, intracellular calcium levels, and endothelial barrier function reflected by transendothelial albumin movement. Both 18:2 and TNF increased cellular oxidation, intracellular calcium, and endothelial barrier permeability. These changes were cross-amplified in cells treated both with 18:2 and TNF, compared with 18:2 or TNF alone. In contrast, a combined exposure to 18:2 and TNF did not potentiate effects mediated by 18:2 or TNF alone on NF-κB activation or NF-κB-related transcription. Pretreatment with 25 μM vitamin E attenuated 18:2 and/or TNF-mediated endothelial cell dysfunction. These results suggest that certain unsaturated fatty acids can potentiate TNF- mediated endothelial cell dysfunction and that oxidative stress may be partially responsible for these metabolic events. These findings have implications for understanding lipid-mediated inflammatory responses in atherosclerosis.

Original languageEnglish
Pages (from-to)123-135
Number of pages13
JournalJournal of Lipid Research
Issue number1
StatePublished - Jan 1996


  • antioxidants
  • atherosclerosis
  • fatty acids
  • inflammatory cytokines
  • intracellular calcium
  • nuclear transcription factors
  • oxidative stress
  • transcription
  • transfection

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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