LDL and apoB
Gemfibrozil enlarges LDL particles and trends toward lowering CETP activity without changing LDL receptor binding (Atherosclerosis 1995)
Original title: Effect of gemfibrozil treatment in hypercholesterolemia on low density lipoprotein (LDL) subclass distribution and LDL-cell interaction
Twelve type IIa hyperlipidemic patients were treated with gemfibrozil for 12 weeks to investigate the mechanism of its cholesterol-lowering effect, with detailed assessment of LDL structure, LDL-receptor interaction, LDL-receptor activity in mononuclear cells, and LCAT and CETP activities. Total and LDL cholesterol fell 17% and 20% respectively, correlating with baseline levels (r = 0.75 and 0.78), mean LDL diameter increased from 25.5 to 26.1 nm, and the proportion of small LDL particles rose from 23.4% to 32.8% of total LDL. Neither apoB secondary structure nor LDL affinity for fibroblast LDL receptors changed, while mononuclear cell LDL-receptor activity rose threefold independent of the cholesterol reduction. LCAT activity was unchanged, and CETP activity fell by 25% though this did not reach significance (P = 0.13). The authors conclude that gemfibrozil alters LDL structure without affecting LDL interaction with peripheral cells.
Original abstract
Gemfibrozil, a widely used fibric acid derivative, corrects hypercholesterolemia in a non-negligible fraction of patients. To investigate the mechanism of the cholesterol-lowering activity of fibric acids, a study was performed in 12 type IIa hyperlipidemic patients treated with gemfibrozil for 12 weeks. Changes in low density lipoprotein (LDL) structure and composition, agonist capacity of LDL against the LDL-receptor in human skin fibroblasts, LDL-receptor activity in mononuclear cells, lecithin:cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, were evaluated. Plasma total and LDL cholesterol levels decreased by 17% and 20% after 12 weeks of treatment, the reduction being directly correlated with the baseline levels (r = 0.75 and 0.78, respectively). The mean LDL diameter increased significantly, from 25.5 to 26.1 nm, while the relative content of small LDL particles (< 25.1 nm) increased from 23.4% to 32.8% of total LDL. Neither the apolipoprotein (apo) B secondary structure nor the affinity of LDL for the LDL-receptor of fibroblasts were affected. The LDL-receptor activity in patients' mononuclear cells increased 3-fold, the rise being unrelated to the plasma cholesterol reduction. LCAT activity did not change, while CETP activity was reduced by 25% (P = 0.13) after treatment. These findings indicate that gemfibrozil causes significant changes in LDL structure that do not, however, affect the LDL interaction with peripheral cells.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.