REGULATION OF HEPATIC HIGH-DENSITY-LIPOPROTEIN BINDING-PROTEINS AFTER ADMINISTRATION OF SIMVASTATIN AND CHOLESTYRAMINE TO RATS

We investigated the regulation of putative high density lipoprotein (HDL) receptors in rat liver after cholesterol feeding and the administration of cholesterol-lowering drugs to rats. The expression of two plasma membrane HDL binding proteins (HB1 and HB2) were compared in control and treated livers by first separating membrane proteins on sodium dodecyl sulfate-polyacrylamide gels and quantitating HB1 and HB2 levels with a specific ligand blot assay. Of the various treatments used, only simvastatin or simvastatin plus cholestyramine produced significant changes, with reductions of up to 40% and 60%, respectively, for HB1 and HB2. The effect on the binding proteins was not associated with changes in serum cholesterol concentrations, which did not change significantly after either treatment, although a marked rise in liver cholesterol concentration after cholesterol was associated with a moderate increase in HB2 expression. We show evidence for regulation of the levels of hepatic HDL binding proteins and provide another important criterion for the acceptance of HB1 and HB2 as components of a functional HDL receptor.