Lipid peroxidation and decomposition--conflicting roles in plaque vulnerability and stability

Biochim Biophys Acta. 2008 May;1781(5):221-31. doi: 10.1016/j.bbalip.2008.03.002. Epub 2008 Mar 25.


The low density lipoprotein (LDL) oxidation hypothesis has generated considerable interest in oxidative stress and how it might affect atherosclerosis. However, the failure of antioxidants, particularly vitamin E, to affect the progression of the disease in humans has convinced even staunch supporters of the hypothesis to take a step backwards and reconsider alternatives. Preponderant evidence for the hypothesis came from animal antioxidant intervention studies. In this review we point out basic differences between animal and human atherosclerosis development and suggest that human disease starts where animal studies end. While initial oxidative steps in the generation of early fatty streak lesions might be common, the differences might be in the steps involved in the decomposition of peroxidized lipids into aldehydes and their further oxidation into carboxylic acids. We suggest that these steps may not be amenable to attenuation by antioxidants and antioxidants might actually counter the stabilization of plaque by preventing the formation of carboxylic acids which are anti-inflammatory in nature. The formation of such dicarboxylic acids may also be conducive to plaque stabilization by trapping calcium. We suggest that agents that would prevent the decomposition of lipid peroxides and promote the formation and removal of lipid hydroxides, such as paraoxonase (PON 1) or apo A1/high density lipoprotein (HDL) might be more conducive to plaque regression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aldehydes / chemistry
  • Aldehydes / metabolism
  • Animals
  • Antioxidants / metabolism
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / metabolism
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Disease Progression
  • Estradiol / metabolism
  • Humans
  • Inflammation
  • Lipid Peroxidation*
  • Lipoproteins, LDL* / chemistry
  • Lipoproteins, LDL* / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Peroxidase / metabolism
  • Risk Factors


  • Aldehydes
  • Antioxidants
  • Carboxylic Acids
  • Lipoproteins, LDL
  • Estradiol
  • Peroxidase