Cholesterol Synthesis and Low Density Lipoprotein Receptor Activity in Mononuclear Cells Freshly Isolated from the Patients with or without Familial Hypercholesterolemia

Abstract

Cholesterol synthesis and LDL receptor activity were examined in circulating human lymphocytes freshly isolated from venous blood ofthe patients with or without familial hypercholesterolemia (FH).
Mononuclear cells were freshly isolated by the method using the Ficoll-Paque^® at 4°C and suspended in RPMI-1640 medium containing 4% bovine fatty acid free albumin. Incorporation from 2-¹⁴C-acetate into digitonin precipitable sterols and proteolytic degradation of ¹²⁵I-LDL at 37°C were measured.
The rate of ¹⁴C-incorporation into sterol was linear with time for at least 3h and the high affinity ¹²⁵I-LDL degradation showed the initial lag phase and the saturable curve in the cells isolated from normal subjects. There was no difference in the rate of cholesterol synthesis among the control, the heterozygous FH and homozygous FH. High affinity ¹²⁵I-LDL degradation from homozygous FH was significantly low (p<0.05), but not in the cells from heterozygous FH in comparison with that from control subjects.¹⁴C-lncorporation into sterol negatively correlated with VLDL-cholesterol (p<0.05). High affinity ¹²⁵I-LDL degradation negatively correlated with LDL-cholesterol (p<0.05).
These results suggest that in vivo LDL receptor activity in the mononuclear cells isolated from hetrozygous FH showed no difference from that in the cells isolated from control subjects, but LDL receptor activity from homozygous FH was significantly low in comparison with that from control subjects. The rate of cholesterol synthesis in the cells from heterozygous FH and from homozygous FH were within the normal range. As there was a significantly negative correlation between cholesterol synthesis and VLDL-cholesterol, the regulation of cholesterol synthesis and LDL receptor activity in circulating human lymphocytes may depend not only on LDL-cholesterol, but on VLDL-cholesterol.