Lipoprotein fractions and receptors: a role for probucol?

Cholesterol transport in the plasma involves several lipoprotein families. The process is remarkably ordered and is driven vectorily by apolipoproteins, which activate appropriate enzymes or serve as recognition sites for lipoprotein receptors. Of the lipoproteins in plasma, low density lipoprotein (LDL) contains most of the cholesterol and has the greatest atherogenic potential. Its plasma concentration is determined by LDL receptor activity, which serves to regulate intracellular cholesterol concentrations. LDL receptor activity in the body is not fixed, but can be stimulated by drugs that affect hepatic cholesterol content, such as inhibitors of HMG-CoA reductase or bile acid sequestrants. By stimulating LDL receptor activity, these drugs increase the fractional catabolic rate of apoLDL. HMG-CoA reductase inhibitors also appear to reduce the apoLDL synthetic rate. As a consequence, LDL cholesterol levels are reduced while high density lipoprotein (HDL) cholesterol levels remain stable or increase. Probucol is a drug that lowers both LDL and HDL cholesterol levels. It appears to lower LDL cholesterol levels by affecting LDL structure rather than by stimulating LDL receptor activity. It has no consistent effect on LDL synthetic rates. Probucol lowers plasma HDL cholesterol levels by decreasing the synthetic rates of the major HDL apolipoproteins. The biologic significance of these probucol-induced changes in HDL metabolism is unknown.