[LDL receptors]

The low density lipoprotein receptor removes the cholesterol-carrying lipoproteins from blood. When the activity of LDL receptors is reduced, as a result of genetic or acquired abnormalities, LDL increases in blood, resulting in atherosclerosis. Heterozygote familial hypercholesterolemia (one mutant gene) is characterized by a 50% reduction of LDL receptors leading to twofold increases of LDL. In homozygote familial hypercholesterolemia (two mutant genes), there are no active LDL receptors. So very high cholesterol blood levels are observed and severe atherosclerosis ensues. FH heterozygotes can be treated with drugs that stimulate the cells to produce more LDL receptors. Because these are under negative feed-back regulation by intracellular cholesterol, depletion of intracellular cholesterol in the liver through administration of bile acid-binding resins and cholesterol synthesis inhibitors activates the synthesis of LDL receptors. The ingestion of a die rich in cholesterol and saturated fatty acids reduce the LDL receptors in the liver. This may contribute in part to the widespread occurrence of high cholesterol levels and atherosclerosis in western societies.