Recent studies suggest that both
oxidized very-low-density lipoprotein (VLDL) and oxidized
high-density lipoprotein (HDL) may play a role in the pathogenesis of
atherosclerosis.
Gemfibrozil is widely used and is reported to decrease VLDL levels and increase HDL levels. The aim of this study was to investigate the effect of
gemfibrozil on the chemical composition and oxidative susceptibility of VLDL and HDL and their relationship with
atherosclerosis. Twenty patients with
hypertriglyceridemia were treated with 300 mg
gemfibrozil, 3 times daily, for 12 weeks. Venous blood samples were collected before treatment, at the end of treatment, and 4 weeks after the end of treatment.
Gemfibrozil effectively lowered concentrations of plasma
lipid,
apolipoprotein (
apo) B, and
apo E. The
lipid and
protein content of VLDL were also decreased, but not by the same extent. The surface-to-core ratio and
apo E/
apo B ratio of VLDL particles were increased after
gemfibrozil treatment.
HDL(2)
cholesteryl ester and HDL(3)
apo A-II content were also increased.
Gemfibrozil treatment lowered levels of
lipid peroxides in both VLDL and HDL particles. The susceptibility of VLDL to oxidation was unchanged, whereas maximal
peroxide production was decreased. The oxidative susceptibility of both
HDL(2) and HDL(3) decreased with
gemfibrozil treatment. These results indicate that after
gemfibrozil treatment, VLDL and HDL particles in patients with
hypertriglyceridemia are less atherogenic, which may explain why
gemfibrozil treatment is beneficial in terms of
coronary heart disease in
hypertriglyceridemia.