Binding of 111In-labeled HDL to platelets from normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.
High density lipoproteins (HDLs; d = 1.063 - 1.21 g/ml) were isolated by ultracentrifugation and radiolabeled with 111In. The in vitro binding onto platelets from healthy volunteers (n = 15) and patients (n = 36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites, which bound 1,882 +/- 361 ng protein of 111In-HDL/10(9) platelets (dissociation constant [Kd] = 7 +/- 3 micrograms protein/ml) in healthy volunteers and significantly (p less than 0.01) lower amounts in the FH patients (1,012 +/- 439 ng protein of 111In-HDL/10(9) platelets [Kd = 12 +/- 4 micrograms protein/ml]; p less than 0.01). The capacity to displace one half of the bound ligand (IC50) amounted to 14 +/- 3 micrograms protein/ml in healthy volunteers and 22 +/- 9 micrograms protein/ml in FH patients (p less than 0.001). Treatment with lipid-lowering drugs (gemfibrozil, alone or in combination with cholestyramine) in 10 patients resulted in an increased HDL binding capacity: before treatment, 1,280 +/- 883; after 2 months of treatment, 2,052 +/- 873 (p less than 0.05); and after 6 months of treatment, 2,127 +/- 812 ng protein/10(9) platelets (p less than 0.01). There was a significant (p less than 0.001) correlation between 111In-HDL binding data and plasmatic lipid and lipoprotein values. Furthermore, those FH patients with the additional risk factors of smoking (p less than 0.05) and hypertension (p less than 0.01) showed significantly lower 111In-HDL binding onto platelets. The findings indicate specific 111In-HDL binding sites for human platelets, which may be decreased in patients with heterozygous FH. Upregulation of HDL binding sites during lipid-lowering medication therapy supports the hypothesis that high-affinity HDL binding is involved in hyperlipemic disorders and is possibly related to the reactivity of platelets.
Virgolini
I
I
Department of Nuclear Medicine, Ludwig Boltzman Institute for Nuclear Medicine, University of Vienna, Austria.
Li
S
S
Yang
Q
Q
Banyai
M
M
Koller
E
E
Angelberger
P
P
Sinzinger
H
H
D000328:Adult; D000368:Aged; D001665:Binding Sites; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007205:Indium Radioisotopes; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D018110:Receptors, Lipoprotein; D012016:Reference Values; D013696:Temperature; D013997:Time Factors
D000960:Hypolipidemic Agents; D007205:Indium Radioisotopes; D008055:Lipids; D008075:Lipoproteins, HDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein