2-Chlorohexadecanal and 2-chlorohexadecanoic acid induce COX-2 expression in human coronary artery endothelial cells

Lipids. 2008 Jul;43(7):581-8. doi: 10.1007/s11745-008-3189-y. Epub 2008 May 21.


2-Chlorohexadecanal (2-ClHDA), a 16-carbon chain chlorinated fatty aldehyde that is produced by reactive chlorinating species attack of plasmalogens, is elevated in atherosclerotic plaques, infarcted myocardium, and activated leukocytes. We tested the hypothesis that 2-ClHDA and its metabolites, 2-chlorohexadecanoic acid (2-ClHA) and 2-chlorohexadecanol (2-ClHOH), induce COX-2 expression in human coronary artery endothelial cells (HCAEC). COX-2 protein expression increased in response to 2-ClHDA treatments at 8 and 20 h. 2-ClHA also increased COX-2 expression following an 8 h treatment. Quantitative PCR showed that 2-ClHDA treatment increased COX-2 mRNA over 8 h, while 2-ClHA treatment led to a modest increase by 1 h and those levels remained constant over 8 h. 2-ClHDA led to a significant increase in 6-keto-PGF(1alpha) release (a measure of PGI(2) release) by HCAEC. These data suggest that 2-ClHDA and its metabolite 2-ClHA, which are produced during leukocyte activation, may alter vascular endothelial cell function by upregulation of COX-2 expression.

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / metabolism
  • Aldehydes / pharmacology*
  • Blotting, Western
  • Cells, Cultured
  • Coronary Vessels / cytology
  • Coronary Vessels / drug effects*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / enzymology
  • Gene Expression Regulation / drug effects*
  • Humans
  • I-kappa B Proteins / metabolism
  • Palmitic Acid / pharmacology*
  • Palmitic Acids / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology


  • 2-chlorohexadecanal
  • 2-chlorohexadecanoic acid
  • Aldehydes
  • I-kappa B Proteins
  • Palmitic Acids
  • Tumor Necrosis Factor-alpha
  • Palmitic Acid
  • 6-Ketoprostaglandin F1 alpha
  • Cyclooxygenase 2