Native and modified low-density-lipoprotein interaction with human platelets in normal and homozygous familial-hypercholesterolaemic subjects

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Abstract
The binding of low density lipoproteins (LDL) as well as LDL modified by cyclohexanedione (CHD-LDL) to gel-filtered platelets (GFP), and its effect on platelet function were studied in normal and in homozygous familial hypercholesterolemic (HFH) subjects [plays a major role in atherosclerosis]. Only normal-derived LDL could significantly compete with normal 125I-labeled LDL for binding to normal platelets. When GFP from normal subjects were incubated with normal LDL at concentrations of 25-200 .mu.g of protein/ml, platelet aggregation in the presence of thrombin (0.5 IU/ml) was increased by 65-186%. CHD-LDL, at similar concentrations, caused the opposite effect and decreased platelet aggregation by 26-47%. Both LDL and CHD-LDL (100 .mu.g/ml) from HFH patients, when incubated with normal GFP, caused a significant reduction in platelet aggregation (33 and 50%, respectively). When HFH-derived platelets were used, both patient LDL and CHD-LDL (but not the normal lipoprotein) could markedly compete with the patient 125I-labeled LDL for binding to the platelets. LDL and CHD-LDL (100 .mu.g/ml) from normal subjects decreased aggregation of HFH-platelets by 52 and 85%, respectively, while corresponding concentrations of LDL derived from HFH subjects (HFH-LDL) and CHD-LDL derived from HFH subjects (CHD-HFH-LDH) increased platelet aggregation by 165 and 65%, respectively. The following conclusions are supported: platelet activation by LDL in normal subjects is through the arginine-rich apoprotein-binding site; more than one binding site for LDL exists on platelets; under certain circumstances, LDL binding can cause a reduction in platelet activity; specificity for LDL binding to the platelets resides in different regions of the lipoprotein in HFH and in normal subjects. A model for LDL-platelet interaction in normal and in HFH subjects was suggested.