title: Binding of 111In-labeled LDL to platelets of normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.
abstract: 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)
authors: Department of Nuclear Medicine, University of Vienna, Austria.
authors: I
authors: I
authors: Virgolini
authors: S
authors: S
authors: Li
authors: Y
authors: Y
authors: Qiong
authors: E
authors: E
authors: Koller
authors: M
authors: M
authors: Banyai
authors: P
authors: P
authors: Angelberger
authors: H
authors: H
authors: Sinzinger
mesh_terms: 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
chemical_list: D000960:Hypolipidemic Agents; D007205:Indium Radioisotopes; D008055:Lipids; D008077:Lipoproteins, LDL