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

I Virgolini, S Li, Y Qiong, E Koller, M Banyai, P Angelberger, H Sinzinger
1993 Arteriosclerosis and Thrombosis A Journal of Vascular Biology  
Low density lipoproteins (LDLs) were isolated by ultracentrifugation and radiolabeled with '"In. 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 '"In-LDL per 10' platelets (dissociation constant [AT d ], 6±3 fig protein/mL) in healthy volunteers and
more » ... cantly (p<0.001) lower amounts in the FH patients (mean, 633±341 ng protein/10 9 platelets; K d , 10±5 fig protein/mL). The capacity of native LDL to displace bound '"In-LDL by half amounted to 10±4 fig protein/mL in volunteers and 22±8 fig protein/mL in FH patients (p<0.001) . Treatment with gemflbrozil alone or in combination with cholestyramine in 10 patients resulted in increased "'In-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 l,272±701 ng protein/10 9 platelets after 6 months of therapy [p<0.01]). Significant correlations between nl In-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 "'In-lipoprotein-specific binding sites on human platelets. Platelets of patients with heterozygous FH express lower numbers of binding sites, which could be upregulated during lipid-lowering intervention. It is concluded that high-affinity LDL binding may involve in vivo processes related to platelet activation in hyperlipemic disorders. (Arteriosclerosis and Thrombosis 1993;13:536-547) KEY WORDS • '"In-LDL • platelets • familial hypercholesterolemia • lipid-lowering drugs From the Departments of Nuclear Medicine (I
doi:10.1161/01.atv.13.4.536 fatcat:6ow5aokeijempibvwvat4sdhoy