Effect of gemfibrozil on the composition and oxidation properties of very-low-density lipoprotein and high-density lipoprotein in patients with hypertriglyceridemia

Recent studies suggest that both oxidized very-low-density lipoprotein (VLD L) and oxidized high-density lipoprotein (HDL) may play a role in the patho genesis of atherosclerosis. Gemfibrozil is widely used and is reported to d ecrease VLDL levels and increase HDL levels. The aim of this study was to i nvestigate the effect of gemfibrozil on the chemical composition and oxidat ive susceptibility of VLDL and HDL and their relationship with atherosclero sis, Twenty patients with hypertriglyceridemia were treated with 300 mg gem fibrozil, 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 tre atment. Gemfibrozil effectively lowered concentrations of plasma lipid, apo lipoprotein (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 a po E/apo B ratio of VLDL particles were increased after gemfibrozil treatme nt. HDL2 cholesteryl ester and HDL3 apo A-ii content were also increased. G emfibrozil 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 HDL2 and HDL3 decreased with gemfibrozil treatment. These results indi cate that after gemfibrozil treatment, VLDL and HDL particles in patients w ith hypertriglyceridemia are less atherogenic, which may explain why gemfib rozil treatment is beneficial in terms of coronary heart disease in hypertr iglyceridemia.