Mildly oxidised LDL induces more macrophage death than moderately oxidised LDL: roles of peroxidation, lipoprotein-associated phospholipase A2 and PPARgamma

Keri L H Carpenter, Iain R Challis, Mark J Arends

Research output: Contribution to journalArticlepeer-review

Abstract

Death of macrophages and smooth muscle cells (SMC) can lead to progression of atherosclerosis. Mildly oxidised low-density lipoprotein (mildly-oxLDL) induced more overall death and apoptosis than moderately oxidised LDL, in human monocyte-macrophages (HMM). Mildly-oxLDL also induced more overall death in human SMC than did moderately-oxLDL. Mildly-oxLDL contained more hydroperoxides, but less oxysterol, malondialdehyde and negative charge than moderately-oxLDL. Specific inhibition of lipoprotein-associated phospholipase A(2) (by SB222657) diminished death induction in HMM by both oxLDL types. Peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist (GW9662) and agonist (ciglitazone) experiments suggested that non-hydrolysed, oxidised phospholipids in oxLDL activate PPARgamma as a cellular defence mechanism. These results may be relevant to LDL oxidation within atherosclerotic plaques and may suggest strategies for combating atherosclerosis progression.
Original languageEnglish
Pages (from-to)145-50
Number of pages6
JournalFEBS Letters
Volume553
Issue number1-2
DOIs
Publication statusPublished - 9 Oct 2003

Keywords

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Apoptosis
  • Humans
  • Lipid Peroxidation
  • Lipoproteins, LDL
  • Macrophages
  • Oxidation-Reduction
  • Phospholipases A
  • Phospholipases A2
  • Receptors, Cytoplasmic and Nuclear
  • Time Factors
  • Transcription Factors

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