EFFECT OF GEMFIBROZIL TREATMENT IN HYPERCHOLESTEROLEMIA ON LOW-DENSITY-LIPOPROTEIN (LDL) SUBCLASS DISTRIBUTION AND LDL-CELL INTERACTION

Gemfibrozil, a widely used fibric acid derivative, corrects hyperchole sterolemia in a non-negligible fraction of patients. To investigate th e mechanism of the cholesterol-lowering activity of fibric acids, a st udy was performed in 12 type IIa hyperlipidemic patients treated with gemfibrozil for 12 weeks. Changes in low density lipoprotein (LDL) str ucture and composition, agonist capacity of LDL against the LDL-recept or in human skin fibroblasts, LDL-receptor activity in mononuclear cel ls, lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activity, were evaluated. Plasma total and LDL cholesterol levels decreased by 17% and 20% after 12 weeks of treatme nt, the reduction being directly correlated with the baseline levels ( r = 0.75 and 0.78: respectively). The mean LDL diameter increased sign ificantly, from 25.5 to 26.1 nm, while the relative content of small L DL particles ( < 25.1 nm) increased from 23.4% to 32.8% of total LDL. Neither the apolipoprotein (ape) B secondary structure nor the affinit y of LDL for the LDL-receptor of fibroblasts were affected. The LDL-re ceptor activity in patients' mononuclear cells increased 3-fold, the r ise being unrelated to the plasma cholesterol reduction. LCAT activity did not change, while CETP activity was reduced by 25% (P = 0.13) aft er treatment. These findings indicate that gemfibrozil causes signific ant changes in LDL structure that do not, however, affect the LDL inte raction with peripheral cells.