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


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.
Vekic
J
J
Institute for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. jelena.vekic@pharmacy.bg.ac.yu
Kotur-Stevuljevic
J
J
Jelic-Ivanovic
Z
Z
Spasic
S
S
Spasojevic-Kalimanovska
V
V
Topic
A
A
Zeljkovic
A
A
Stefanovic
A
A
Zunic
G
G
D043303:Aryldialkylphosphatase / Q000097:blood*; D050197:Atherosclerosis / Q000453:epidemiology / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010316:Particle Size; D012307:Risk Factors
D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human