Comparison of iodine-123 low-density lipoprotein (LDL) and indium-111 LDL binding to mononuclear cells of healthy normolipaemic controls and patients with heterozygous familial hypercholesterolaemia.
The binding of radiolabelled lipoproteins, iodine-123-labelled low-density lipoprotein (LDL) and indium-111-labelled LDL, to peripheral blood mononuclear cells (MNCs) was compared in normolipaemic subjects and in patients with heterozygous familial hypercholesterolaemia (FH). 123I-LDL and 111In-LDL binding to MNCs exhibited high-affinity, highly specific, time- and temperature-dependent binding reaching saturation at concentrations above 50 nM. The number of LDL binding sites (Bmax) was significantly (P < 0.01) lower in FH patients (P < 0.001; 123I-LDL: Bmax 279 +/- 44 ng protein/10(8) MNCs; 111In-LDL: Bmax 309 +/- 43 ng protein/10(8) MNCs) as compared with controls (123I-LDL: Bmax 2874 +/- 246 ng protein/10(8) MNCs; 111In-LDL: Bmax 3145 +/- 339 ng protein/10(8) MNCs). The corresponding dissociation constants (Kd) were 16 +/- 8 nM for 123I-LDL and 12 +/- 6 nM for 111In-LDL in healthy volunteers (123In-LDL vs 111In-LDL, P < 0.05). In FH patients, the Kd values were 20 +/- 8 nM for 123I-LDL and 16 +/- 6 nM for 111In-LDL (P < 0.05 vs controls for both 123I-LDL and 111In-LDL). 111In-LDL binding to MNCs was inhibited (IC50) by 30 +/- 8 nM in healthy controls and 38 +/- 12 nM in FH patients (P < 0.05). 123In-LDL binding to MNCs was inhibited (IC50) by 34 +/- 8 nM in healthy controls and 46 +/- 10 nM in FH patients (P < 0.05). Taken together, these results suggest a reduced number of LDL receptors expressed on MNCs from FH patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Nuclear Medicine, University of Vienna, Austria.
M
M
Banyai
G
G
Lupattelli
S R
SR
Li
S
S
Pongratz
Q
Q
Yang
P
P
Böck
P
P
Angelberger
I
I
Virgolini
D001665:Binding Sites; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000378:metabolism; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D011973:Receptors, LDL / Q000032:analysis* / Q000378:metabolism; D013997:Time Factors
D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL