We altered platelet cholesterol by incubating the cells with either "cholesterol-rich" or "cholesterol-poor" liposomes. These platelets were then used to study the influence of cholesterol content on the metabolism of arachidonic acid, a fatty acid that serves as the critical precursor in the platelet for formation of the potent aggregating agent thromboxane A2. After addition of the aggregating agent thrombin, cholesterol-enriched platelets released 18.1 +/- 0.6 per cent (mean +/- 1 S.E.M.) [14C]arachidonic acid from prelabeled platelet phospholipids. This value was higher (P less than 0.001) than that for cholesterol-depleted platelets (14.6 +/- 1.0 per cent). Conversion of released arachidonic acid to platelet thromboxane B2 (the stable end product of thromboxane A2) was also higher in cholesterol-rich platelets (22.6 +/- 3.9 per cent) than in cholesterol-depleted platelets (13.8 +/- 2.7 per cent). These studies show that changes in the cholesterol content of human platelets in vitro have a significant effect on platelt metabolism of arachidonic acid. N Engl J Med 302:6-10, 1980).
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