Lowering of serum cholesteryl ester transfer protein--but not lecithin:cholesterol acyltransferase--activity levels by hypocholesterolemic drugs in the rabbit.

Abstract

Cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) are important factors in the regulation of serum lipoprotein metabolism. Rabbits were fed hypocholesterolemic drugs to investigate the effect on serum CETP and LCAT activity levels. The activities were assayed using exogenous substrate assays and are an estimate of CETP and LCAT mass. Groups of eight rabbits were fed a cholesterol-free diet containing either 0.03% simvastatin or 1% cholestyramine for 6 weeks. For comparison eight rabbits were fed a cholesterol-free control diet without drugs or a diet containing 0.1% cholesterol for 6 weeks. Total serum and lipoprotein triglyceride concentrations were not different after intervention with the hypocholesterolemic drugs or the cholesterol diet. Dietary cholesterol induced higher VLDL, IDL, and LDL cholesterol, as well as serum CETP activity, as expected. Serum LCAT activity showed little change with intervention. Both simvastatin and cholestyramine tended to lead to decreased cholesterol in all lipoprotein fractions and caused a significant decrease in serum CETP activity when compared with the control diet. Both drugs also caused a significant lower LDL particle concentration, as judged from differences in LDL protein levels. Intervention with simvastatin or cholestyramine led to relatively cholesterol-poor LDL. These effects on LDL concentration and composition were opposite from the effects of cholesterol feeding. Differences in the cholesterol contents of VLDL and IDL were comparable with those in LDL. The results suggest that decreasing serum CETP activity levels by treatment with simvastatin or cholestyramine may contribute to lowering of cholesterol apo B-containing lipoproteins. The effects are additional to the well-known increase in hepatic LDL receptor activity, which is likely to be the most important factor in LDL cholesterol lowering by these drugs.