Association of oxidative stress and PON1 with LDL and HDL particle size in middle-aged subjects

Eur J Clin Invest. 2007 Sep;37(9):715-23. doi: 10.1111/j.1365-2362.2007.01849.x.


Background: Alterations in plasma lipoprotein subclass distributions affect atherosclerosis risk. Smaller, denser low-density lipoprotein (LDL) particles (sdLDL) are more susceptible to oxidation. In contrast, most of the protective effects of high-density lipoproteins (HDL) are attributable to larger particles. This study investigates the connection between LDL and HDL particle heterogeneity and oxidative stress, antioxidative defence (AOD) and paraoxonase (PON1) status in a healthy middle-aged Serbian population.

Materials and methods: LDL and HDL particle sizes and subclass distributions were measured by gradient gel electrophoresis in 104 men and 103 women, aged 53 +/- 9.4 years. PON1 activities and PON1(Q192R) phenotypes were determined with paraoxon and diazoxon as substrates. The oxidative stress/AOD status was estimated by measuring malondialdehyde (MDA) and superoxide-anion (O2*(-)) levels and superoxide-dismutase (SOD) activity.

Results: Subjects with sdLDL had significantly higher MDA (P < 0.001) and O2*(-)(P < 0.05) levels and greater diazoxonase (DZOase) activity (P < 0.05) compared to subjects with larger LDL particles. A high MDA concentration was a significant predictor of the sdLDL phenotype (P < 0.005). Increased levels of and MDA were associated with smaller HDL(3) subclass abundance. Reduced HDL particle size was associated with lower DZOase activity (P < 0.01).

Conclusions: Even in the absence of symptoms of atherosclerosis, sdLDL particles are associated with increased oxidative stress, which may stimulate a compensatory rise in PON1 DZOase activity. Elevated oxidative stress may significantly affect HDL subclass distribution, resulting in the accumulation of smaller, denser HDL particles with diminished antioxidative capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryldialkylphosphatase / blood*
  • Atherosclerosis / epidemiology
  • Atherosclerosis / metabolism*
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / metabolism*
  • Female
  • Humans
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / metabolism*
  • Male
  • Middle Aged
  • Oxidative Stress / physiology*
  • Particle Size
  • Risk Factors


  • Cholesterol, LDL
  • Lipoproteins, HDL
  • Aryldialkylphosphatase
  • PON1 protein, human