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 receptor 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 of circulating mononuclear cells would reflect the changes seen in liver. 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 22 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 mononuclear cells by 69% and 58%, respectively. In the cholesterol-fed rabbit, pravastatin decreased plasma cholesterol by 55%, liver membrane cholesterol by 29% and bile cholesterol saturation by 23%, and increased liver and mononuclear cell LDL receptor activities by 120% and 77%, respectively. Similarly, simvastatin decreased plasma cholesterol by 74%, liver membrane cholesterol by 24% and bile cholesterol saturation by 38%, and increased liver and mononuclear cell LDL receptor activities by 80% and 62%, respectively. Liver and mononuclear cell LDL receptor activities were directly correlated (r = 0.73, P < 0.005) and both activities were inversely correlated with plasma cholesterol concentration 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 therefore reflected the hepatic LDL receptor activity in these rabbits.