title: Unsaturated fatty acids selectively induce an inflammatory environment in human endothelial cells.
abstract: BACKGROUND
  Activation of the vascular endothelium by dietary fatty acids may be among the most critical early events in the development of atherosclerosis. However, the specific effects of fatty acids on inflammatory responses in endothelial cells are not fully understood.
  
  
  OBJECTIVE
  The present study focused on the induction of inflammatory genes in human endothelial cells exposed to individual dietary fatty acids. Because of the significance of nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) in the regulation of inflammatory gene expression, we also determined the effects of fatty acids on NF-kappaB and AP-1 transcriptional activation.
  
  
  METHODS
  Human umbilical vein endothelial cells were exposed to dietary mono- and polyunsaturated 18-carbon fatty acids. Transcriptional activation of NF-kappaB and AP-1 was determined in human umbilical vein endothelial cells transfected with reporter constructs regulated by these transcription factors. Induction of the inflammatory genes was studied by use of reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  Of the fatty acids studied, linoleic acid stimulated NF-kappaB and AP-1 transcriptional activation the most. In addition, treatment with this fatty acid markedly enhanced messenger RNA levels of tumor necrosis factor alpha, monocyte chemoattractant protein 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1. Treatment with linolenic acid stimulated only a moderate induction of the genes encoding for these inflammatory mediators, and exposure to oleic acid either had no effect or resulted in decreased inflammatory gene messenger RNA. In addition, exposure to both linoleic and linolenic acids strongly stimulated induction of the phospholipid hydroperoxide glutathione peroxidase gene.
  
  
  CONCLUSIONS
  Specific unsaturated dietary fatty acids, particularly linoleic acid, can selectively stimulate the development of a proinflammatory environment within the vascular endothelium.
authors.affiliation: Department of Surgery, University of Kentucky Medical Center, Lexington 40536, USA. mjtobo00@pop.uky.edu
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.forename: Rosario
authors.initials: R
authors.lastname: Garrido
authors.forename: Simone
authors.initials: S
authors.lastname: Kaiser
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hennig
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014471:Umbilical Veins
chemical_list: D005231:Fatty Acids, Unsaturated; D016328:NF-kappa B; D014157:Transcription Factors