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


  • (

    Institute for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia J. Vekic, J. Kotur- Stevuljevic, Z. Jelic-Ivanovic, S. Spasic, V. Spasojevic- Kalimanovska, A. Topic, A. Zeljkovic, A. Stefanovic); Institute for Medical Investigation, Military Medical Academy, Belgrade, Serbia (G. Zunic).

Jelena Vekic, Institute for Medical Biochemistry, Faculty of Pharmacy, Vojvode Stepe 450, P. Box 146, 11000 Belgrade, Serbia. Tel.: + 381 11 39-70-379; fax: + 381 11 39-72-840 or + 381 11 39-74-349; e-mail:


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 PON1Q192R phenotypes were determined with paraoxon and diazoxon as substrates. The oxidative stress/AOD status was estimated by measuring malondialdehyde (MDA) and superoxide-anion (inline image) levels and superoxide-dismutase (SOD) activity.

Results  Subjects with sdLDL had significantly higher MDA (P < 0·001) and inline image (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 inline image and MDA were associated with smaller HDL3 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.