Lipid peroxidation in low density lipoproteins from human plasma and egg yolk promotes accumulation of 1-acyl analogues of platelet-activating factor-like lipids

Lipids. 1996 Dec;31(12):1251-8. doi: 10.1007/BF02587909.

Abstract

Oxidative modification of low density lipoprotein (LDL) is known to be a key event for induction of atherosclerosis. However, there has been little progress in structural elucidation of oxidized lipids, especially oxidatively fragmented phospholipids retaining a glycerol backbone. In this study, we found that LDL derived from egg yolk has no platelet-activating factor (PAF) acetylhydrolase activity, and that prolonged incubation of egg yolk LDL with Cu2+ resulted in the formation of various PAF-like lipids: 1-acyl type phosphatidylcholines with an sn-2-short-chain dicarboxylate or monocarboxylate group. Only a very small amount of the PAF-like lipid having an sn-2-short-chain monocarboxylate group was detected by gas chromatography-mass spectrometry in Cu(2+)-oxidized LDL from human plasma with high PAF-acetylhydrolase activity, which has been reported to hydrolyze PAF-like lipids to lysophosphatidyl-cholines. Preincubation of plasma LDL with diisopropyl fluorophosphate dose-dependently inhibited PAF-acetylhydrolase activity, resulting in accumulation of the PAF-like lipids when the LDL was oxidized with Cu2+. As well as PAF and lysophosphatidylcholines, several PAF-like lipids were found to inhibit [3H]thymidine incorporation into cultured vascular smooth muscle cells derived from rat aorta. The possible formation of PAF-like lipids by lipid peroxidation in LDL is discussed as well as its possible significance for induction of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Animals
  • Cells, Cultured
  • Chickens
  • Egg Yolk / chemistry
  • Female
  • Humans
  • In Vitro Techniques
  • Lipid Metabolism*
  • Lipid Peroxidation*
  • Lipids / chemistry
  • Lipids / toxicity
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / metabolism*
  • Molecular Structure
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Phosphatidylcholines / chemistry
  • Phosphatidylcholines / metabolism
  • Platelet Activating Factor / analogs & derivatives*
  • Platelet Activating Factor / chemistry
  • Platelet Activating Factor / metabolism
  • Rats
  • Spectrometry, Mass, Fast Atom Bombardment
  • Thymidine / metabolism

Substances

  • Lipids
  • Lipoproteins, LDL
  • Phosphatidylcholines
  • Platelet Activating Factor
  • Thymidine