THE ROLE OF (E)-4-HYDROXY-2-NONENAL IN PLATELET ACTIVATION BY LOW-DENSITY-LIPOPROTEIN AND IRON

(E)-4-Hydroxy-2-nonenal (HNE) is a highly reactive product of the oxid ation of low density lipoprotein (LDL) which increases the platelet ag gregation response to various agonists. HNE formation was increased du ring the enhanced platelet aggregation to thrombin, ADP, A23187 and ep inephrine in the presence of LDL. The increase in platelet aggregation and HNE formation by LDL was inhibited by superoxide dismutase and ca talase, suggesting superoxide and hydrogen peroxide produced by platel ets during aggregation may be at least partly responsible. The respons iveness of platelets to LDL and the accompanying HNE formation was inc reased further in the presence of ferrous ion. The effect of ferrous i on on both platelet responses and HNE formation was decreased by super oxide dismutase, catalase and the antioxidants dipyridamole and probuc ol implicating platelet-derived free radicals. Ferrous ion caused an i ncrease in the release of arachidonic acid from platelet membrane phos pholipids in the presence of LDL which was probably caused by increase d HNE production. The results suggest iron could increase platelet rea ctivity at sites of vascular injury by increasing HNE formation and pr omote the development of atherosclerotic lesions. (C) 1998 Elsevier Sc ience Ireland Ltd. All rights reserved.