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

作者:Vekic J*; Kotur Stevuljevic J; Jelic Ivanovic Z; Spasic S; Spasojevic Kalimanovska V; Topic A; Zeljkovic A; Stefanovic A; Zunic G
来源:European Journal of Clinical Investigation, 2007, 37(9): 715-723.
DOI:10.1111/j.1365-2362.2007.01849.x

摘要

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 (O-2(.-)) levels and superoxide-dismutase (SOD) activity.
Results Subjects with sdLDL had significantly higher MDA (P < 0.001) and O-2(.-) (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 O-2(.-) 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.