COORDINATE CHANGES IN THE LOW-DENSITY-LIPOPROTEIN RECEPTOR ACTIVITY OF LIVER AND MONONUCLEAR-CELLS IN THE RABBIT

In the rabbit, dietary cholesterol downregulates the hepatic LDL recep tor and concomitant treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors partly restores its expression. The aim of this study was to determine whether the LDL receptor activity o f circulating mononuclear cells would reflect the changes seen in live r. New Zealand White rabbits were fed for 3 weeks either a normal diet or diets containing 0.25% (w/w) cholesterol, 0.25% cholesterol plus 2 2 mg/kg per day pravastatin or 0.25% cholesterol plus 6 mg/kg per day simvastatin. Dietary cholesterol increased plasma cholesterol 8.9-fold , liver membrane cholesterol 1.8-fold and bile cholesterol saturation 2.3-fold, and decreased the LDL receptor activities of liver and monon uclear cells by 69% and 58%, respectively. In the cholesterol-fed rabb it, pravastatin decreased plasma cholesterol by 55%, liver membrane ch olesterol by 29% and bile cholesterol saturation by 23%, and increased liver and mononuclear cell LDL receptor activities by 120% and 77%, r espectively. Similarly, simvastatin decreased plasma cholesterol by 74 %, liver membrane cholesterol by 24% and bile cholesterol saturation b y 38%, and increased liver and mononuclear cell LDL receptor activitie s by 80% and 62%, respectively. Liver and mononuclear cell LDL recepto r activities were directly correlated (r = 0.73, P < 0.005) and both a ctivities were inversely correlated with plasma cholesterol concentrat ion in a log-linear fashion (r = -0.70, P < 0.005 and r = -0.69, P < 0 .01, respectively). The LDL receptor activity of mononuclear cells the refore reflected the hepatic LDL receptor activity in these rabbits.