OXIDIZED LOW-DENSITY-LIPOPROTEIN INCREASES U937 CELL 5-LIPOXYGENASE ACTIVITY - INDUCTION OF 5-LIPOXYGENASE ACTIVATING PROTEIN

This study examines the effects of oxidized low density lipoprotein (ox-LDL) on mononuclear cell arachidonic acid (AA) metabolism. U937 and HL60 cells, employed as models for mononuclear cells and promyelocytic cells, respectively, were exposed to ox-LDL (20 mu g protein/ml) for 24 hours. HPLC analysis of 1-C-14-AA metabolites indicates that ox-LDL increases U937 and HL60 cell production of 15-hydroxyeicosatetraenoic acid (15-HETE) and 5-hydroxyeicosatetraenoic acid (5-HETE). Northern analysis indicates that ox-LDL increases U937 cell FLAP transcript levels 10-times control levels but did not appear to alter 5-lipoxygenase (5-LO) mRNA levels. In contrast, ox-LDL increases HL60 cell transcript levels for FLAP and 5-LO 1.5 times and 10 times control. levels, respectively. Thus, we propose that ox-LDL plays an important role in the up-regulation of the 5-LO pathway;in mononuclear cells. Such activation may explain, in part, the mechanisms by which ox-LDL promotes atherogenesis. (C) 1994 Academic Press, Inc.