Abnormal plasma lipoprotein composition in hypercholesterolaemic patients induces platelet activation

Increased platelet activation has been shown to be a feature of patients with familial hypercholesterolaemia. Plasma lipoprotein concentration and composition were studied in eleven male patients with familial hypercholesterolaemia and in ten age-matched healthy controls. Increased levels of cholesterol were found in very-low- and low-density lipoproteins (53 and 275%, respectively), whereas in high-density lipoprotein, both cholesterol and apolipoprotein A-I were decreased by 21 and 26%, respectively. On incubation of gel-filtered platelets derived from normolipidaemic controls with identical concentrations of lipoproteins derived from either nomolipidaemic controls or hypercholesterolaemic patients very-low- and low-density lipoproteins from the patients caused significantly greater thrombin-induced platelet aggregation (P less than 0.01). High-density lipoprotein from normal subjects reduced platelet release by 22%, whereas the patients' high-density lipoprotein had no significant effect on platelet release. Lipoprotein-deficient plasma from both groups augmented platelet function to a similar extent. Lipoprotein composition has an important effect on platelet function in vitro. The abnormal lipid and protein composition of the lipoproteins derived from hypercholesterolaemic patients appears to be the cause of platelet hyperactivity observed in these patients.