Platelet hypersensitivity induced by cholesterol incorporation

Abstract

Platelets from individuals with familial hypercholesterolemia show increased sensitivity to the aggregating agents, epinephrine and adenosine diphosphate (ADP). Since the mechanism of this abnormal sensitivity is unknown, the influence of the plasma lipid environment on the function of platelets was examined in vitro. The composition of plasma lipids was altered by the addition of sonicated cholesterol dipalmitoyl lecithin liposomes which were 'cholesterol normal' (cholesterol phospholipid mole ratio [C/P] = 1.0), 'cholesterol rich' (C/P = 2.2), or 'cholesterol poor' (C/P = 0). Cholesterol normal liposomes had no influence on platelet lipids or platelet function. In contrast, after incubation for 5 hr at 37°C with cholesterol rich liposomes, normal platelets acquired 39.2% excess cholesterol with no change in phospholipids or protein. The percentage increase in platelet membrane cholesterol was 3 fold that of the granule fraction. The acquisition of cholesterol by platelets was associated with a 35 fold increase in sensitivity to epinephrine induced aggregation (P < 0.001) and 15 fold increase to ADP aggregation (P < 0.01), as determined both by aggregometry and by [14C]serotonin release. Platelets incubated with cholesterol poor liposomes underwent a selective loss of 21.4% cholesterol, and this was associated with an 18 fold reduction in their sensitivity to epinephrine.