Binding of In-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 '"In. The in vitro binding onto platelets from healthy volunteers (it=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 '"In-HDL/lC platelets (dissociation constant [£d]=7±3 fig protein/ml) in healthy volunteers and significantly (p<0.01) lower amounts in the FH patients (1,012±439 ng protein of In-HDL/10' platelets [Ki=12±4 fig protein/ml]; /?<0.01). The capacity to displace one half of the bound ligand (ICM) amounted to 14±3 /ig protein/ml in healthy volunteers and 22 ±9 fig protein/ml in FH patients (p< 0.001). Treatment with lipid-lowering drugs (gemfibrozll, 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<0.05); and after 6 months of treatment, 2,127±812 ng protein/10* platelets (p<0.01). There was a significant (p<0.001) correlation between "'In-HDL binding data and plasmatic lipid and lipoprotein values. Furthermore, those FH patients with the additional risk factors of smoking (p<0.05) and hypertension (p<0.01) showed significantly lower "'In-HDL binding onto platelets. The findings indicate specific '"In-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. (Arteriosclerosis and Thrombosis 1992;12:849-861)