Binding of 111In-labeled LDL to platelets of normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.
Low density lipoproteins (LDLs) were isolated by ultracentrifugation and radiolabeled with 111In. The in vitro binding of these radiolabels onto platelets of normolipemic volunteers (n = 15) and patients (n = 36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites capable of binding 1,757 +/- 289 ng protein of 111In-LDL per 10(9) platelets (dissociation constant [Kd], 6 +/- 3 micrograms protein/mL) in healthy volunteers and significantly (p < 0.001) lower amounts in the FH patients (mean, 633 +/- 341 ng protein/10(9) platelets; Kd, 10 +/- 5 micrograms protein/mL). The capacity of native LDL to displace bound 111In-LDL by half amounted to 10 +/- 4 micrograms protein/mL in volunteers and 22 +/- 8 micrograms protein/mL in FH patients (p < 0.001). Treatment with gemfibrozil alone or in combination with cholestyramine in 10 patients resulted in increased 111In-LDL binding by platelets (470 +/- 307 [mean +/- SD] ng protein/10(9) platelets before therapy, 948 +/- 650 ng protein/10(9) platelets after 2 months of therapy [p < 0.01], and 1,272 +/- 701 ng protein/10(9) platelets after 6 months of therapy [p < 0.01]). Significant correlations between 111In-LDL binding capacity and apolipoprotein B (r = -0.83, p < 0.001) and LDL cholesterol (r = -0.80, p < 0.000) concentrations were found. Patients with clinically manifested atherosclerosis (p < 0.01) and those with diabetes mellitus (p < 0.05) had significantly lower platelet LDL binding sites. The findings demonstrate 111In-lipoprotein-specific binding sites on human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Virgolini
I
I
Department of Nuclear Medicine, University of Vienna, Austria.
Li
S
S
Qiong
Y
Y
Koller
E
E
Banyai
M
M
Angelberger
P
P
Sinzinger
H
H
D000328:Adult; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007205:Indium Radioisotopes; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010979:Platelet Function Tests; D012016:Reference Values
D000960:Hypolipidemic Agents; D007205:Indium Radioisotopes; D008055:Lipids; D008077:Lipoproteins, LDL