Diverse Actions of Human Lipoproteins on Arachidonic Acid Metabolism

Abstract

Products of arachidonic acid (AA) metabolism i.e. prostaglandins (PGs), prostacyclin, thromboxane-A₂ (TXA₂) and lipoxygenase metabolites play an important role in platelet aggregation leading to ischemic heart disease and thrombosis. Since lipoproteins are intimately involved in thromboembolic phenomena, we investigated the effects of human lipoproteins (HDL, LDL, VLDL) on metabolism. Lipoproteins were separated by density gradient zonal ultracentrifugation. The effects of lipoproteins on the synthesis of various PGs by isolated PG synthase were measured using radioimmunoassays. The effects of lipoproteins on production of AA metabolites by human platelets i.e. TXA₂ and hydroxyeicosa-tetraenoic acids (HETEs) was examined using radiometric thin layer chromatography coupled with automated data integrator system. All three lipoproteins produced concentration-related inhibition of PG biosynthesis. Relative to HDL and LDL; VLDL was five times more potent in inhibiting PGE₂ synthesis. All three lipoproteins also exerted an inhibitory influence on the production of PGF_2a although not in a concentration related manner. In human platelets, HDL inhibited 12-HETE and TXA₂ in concentration-related manner. LDL had a strong inhibitory effect on TXA₂ production and had a weak inhibitory effect against 12-HETE production. VLDL had no effect on platelet AA metabolism. These findings point to a new facet of lipoproteins action which may have a role in the pathophysiology of thromboembolic disorders.

Represents person presenting Paper