Mildly oxidised LDL induces more macrophage death than moderately oxidised LDL:: roles of peroxidation, lipoprotein-associated phospholipase A2 and PPARγ

Death of macrophages and smooth muscle cells (SMC) can lead to progression of atherosclerosis. Mildly oxidised low-density lipoprotein (mildly-oxLDL) induced more overall death and apoptosis than moderately oxidised LDL, in human monocyte-macrophages (HMM). Mildly-oxLDL also induced more overall death in human SMC than did moderately-oxLDL. Mildly-oxLDL contained more hydroperoxides, but less oxysterol, malondialdehyde and negative charge than moderately-oxLDL. Specific inhibition of lipoprotein-associated phospholipase A(2) (by SB222657) diminished death induction in HMM by both oxLDL types. Peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist (GW9662) and agonist (ciglitazone) experiments suggested that non-hydrolysed, oxidised phospholipids in oxLDL activate PPARgamma as a cellular defence mechanism. These results may be relevant to LDL oxidation within atherosclerotic plaques and may suggest strategies for combating atherosclerosis progression. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.