Characterization of LDL-receptors of freshly isolated mononuclear cells of healthy subjects and of FH-patients

The central role of the LDL (=low density lipoproteins) receptor in artherosclerosis was first appreciated when it was shown that its absence was responsible for FH (familial hypercholesterolemia). To determine the high affinity cell surface binding activity in circulating human mononuclear cells (MNCs), these cells were incubated with low concentrations (1-50 μg protein/ml) of 123I-LDL or 111In-LDL either in the presence or absence of an excess of unlabeled LDL at 4 deg C for 45 minutes. MNCs of healthy subjects and of heterozygous FH-patients were found to possess high affinity LDL receptors immediately after they were isolated from the blood stream. The results indicate that the FH-patients enclosed in this study possess a reduced number of the same high affinity binding sites as healthy subjects confirming the diagnosis of heterozygous FH. In this study 123I-LDL binding and 111In-LDL binding to MNCs has been shown to saturable, reversible and displaceable and time-dependent. 123I-LDL and 111In-LDL as well can be recommended for the in-vitro determination of LDL-receptor binding activity as both binding processes show approximately the same characteristics. (author)