Phospholipase A₂-catalysed modification of plasma low density lipoproteins caused reduction of hypercholesterolemic rabbit plasma cholesterolin vivo

Abstract

Phospholipase A₂ (PLA₂) hydrolyses certain phospholipids of low density lipoproteins. PLA₂-treated LDL is known to be rapidly cleared from plasma. A prototype plasma filter containing immobilizedCrotalus atrox PLA₂ on agarose beads was developed. After a 90 min treatment with the extracorporeal device, plasma cholesterol concentration in cholesterol-fed NZW rabbits decreased by 32%. The decrease was dependent on the enzymatic activity in the plasma filter. The decrease in plasma cholesterol of hypercholesterolemic rabbits that were treated with control reactors (agarose beads only) was 5%. White and red blood cell counts and platelets remained unchanged during the treatment. Plasma cholesterol reduction (25–40%) was also obtained following intravenous injection of active PLA₂ to modify plasma lipoproteins. PLA₂ infusion created a radical change in biliary composition. Bile phospholipid composition was 90–95% lysophosphatidylcholine as compared with more than 95% before injection of active PLA₂. Phospholipid and bile salts total mass increased by 10%. While biliary secretion rate of protein increased by 10%, biliary secretion rate of cholesterol remained unchanged. This technique is specific for lipoproteins, does not require any fluid replacement of sorbent regeneration, and offers a potential new approach for lowering serum cholesterol and LDL levels.