Detection and biological activities of carboxyethylpyrrole ethanolamine phospholipids (CEP-EPs)

Chem Res Toxicol. 2014 Dec 15;27(12):2015-22. doi: 10.1021/tx500216a. Epub 2014 Nov 19.

Abstract

Oxidation of docosahexaenoate phospholipids produces 4-hydroxy-7-oxo-hept-5-eonyl phospholipids (HOHA-PLs) that react with protein lysyl ε-amino residues to generate 2-ω-carboxyethylpyrrole (CEP) derivatives, endogenous factors that induce angiogenesis in the retina and tumors. It seemed likely, but remained unproven, that HOHA-PLs react with ethanolamine phospholipids (EPs) in vivo to generate CEP-EPs. We now show that CEP-EPs are present in human blood at 4.6-fold higher levels in age-related macular degeneration plasma than in normal plasma. We also show that CEP-EPs are pro-angiogenic, inducing tube formation by human umbilical vein endothelial cells by activating Toll-like receptor 2. CEP-EP levels may be a useful biomarker for clinical assessment of AMD risk and CEP-associated tumor progression and a tool for monitoring the efficacy of therapeutic interventions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Liquid
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Macular Degeneration / blood
  • Magnetic Resonance Spectroscopy
  • Phosphatidylethanolamines / blood*
  • Phospholipids / blood*
  • Phospholipids / physiology
  • Tandem Mass Spectrometry

Substances

  • Phosphatidylethanolamines
  • Phospholipids
  • phosphatidylethanolamine