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Phospholipase A2(PLA2) could be the rate-limiting enzyme in the metabolism of arachidonic acid (AA) derived from membrane phospholipid to thromboxane A2 (TXA2). Mal- ondialdehyde (MDA) production, which is considered to be an index of TXA2 synthesis, is increased in platelets which have been enriched in cholesterol by incubation with cholesterol-rich phospholipid dispersions in vitro.  Rabbits were fed a diet supplemented with 0.5% w/w cholesterol for 4 weeks after which serum cholesterol was determined and the platelets examined and compared with rabbits fed a control diet. The cholesterol:phospholipid molar ratio (c/p) in the platelets, MDA production (stimulated by AA (imM) and basal) and PLA2 activity were estimated. PLA2 activity was estimated by measuring the % inversion by resuspended washed platelets of 1-acyl-2-(l- 14C)arachidonyl phosphatidylcholine to (1- 14C)arachidonic acid on stimulation with collagen (2μg/ml). Serum cholesterol in the cholesterol-fed group (n=9) was 488 ± 104 mg/ 100ml compared with the control group (n=3) which was 34 ± 4.7 mg/l00ml. Platelets from the cholesterol-fed rabbits showed a 20% increase in C/P (p&lt;0.05); basal and AA stimulated MDA production was increased by 40% and 27% respectively compared with platelets from the control group. PLA2 activity was 1.26% conversion to products in the cholesterol-enriched platelets compared with 0.10% in the control platelets. This increase in activity was significant (p &lt; 0.05).  These results suggest that increased AA metabolism in cholesterol-enriched platelets may in part be due to increased PLA2 activity. This may reflect a physical effect of cholesterol on the platelet membrane predisposing arachidonyl phosphatidylcholine to PLA2 catalysed hydrolysis.

Enhanced Phospholipase A2 Activity In Cholesterol-Enriched Platelets From Rabbits Fed A Cholesterol-Enriched Diet