Role of the Low Density Lipoprotein Receptor

A B S TRA CT The transfer of normal human fibroblasts from medium containing whole serum to medium devoid of lipoproteins produced a 90% decrease in the cellular content of cholesteryl esters and a 30% decrease in the free cholesterol content. When these lipoproteindeprived cells were subsequently incubated with human low density lipoprotein (LDL), there was a 7-fold increase in the cellular content of esterified cholesterol and a 1.6-fold increase in the cellular content of free cholesterol. The concentration at which LDL produced its half-maximial effect in elevating cellular sterol content (30 yg/ml of LDL-cholesterol) was similar to the half-maximal concentration previously reported for high affinity binding of LDL to its cell surface receptor. High density lipoprotein (HDL) and whole serum from a patient with abetalipoproteinemia (neither of which contains a component that binds to the LDL receptor) did not produce a significant increase in the content of either cholesterol or cholesterYl esters in normal cells. Furthermore, in fibroblasts from patients with the honmozygous form of familial hypercholesterolemia, which lack functional LDL receptors, LDL had no effect in raising the cellular content of either free or esterified cholesterol even when present in the medium at concentrations as high as 450 iyg sterol/nml. It is concluded that LDL-receptor interactions constitute an important biochemical mechanism for the regulation of the cholesterol content of normal human fibroblasts. Mforeover, when considered in light of current concepts of LDL metabolism in intact mammnals, the present data suggest that a major function of