Binding of 111In-labeled LDL to platelets of normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.

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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)