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

FEBS Letters

Challis, Iain R¹  Arends, Mark J¹  Carpenter, Keri L.H¹ 

[1] University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK

关键词: Cell death;    Oxidized low-density lipoprotein;    Peroxidation;    Lipoprotein-associated phospholipase A2;    Peroxisome proliferator-activated receptor γ;    Monocyte-macrophage (human);    AO;    acridine orange;    15d-PGJ2;    15-deoxy-Δ12;    14-prostaglandin J2;    ELISA;    enzyme-linked immunosorbent assay;    FCS;    foetal calf serum;    FOX;    ferrous oxidation of xylenol orange;    GC;    gas chromatography;    HMM;    human monocyte-macrophages;    LDH;    lactate dehydrogenase;    LDL;    low-density lipoprotein;    Lp-PLA2;    lipoprotein-associated phospholipase A2;    lyso-PC;    lysophosphatidylcholine;    MDA;    malondialdehyde;    NA;    no additions;    natLDL;    native low-density lipoprotein;    oxLDL;    oxidised low-density lipoprotein;    ox(1)LDL;    ox(2)LDL and ox(3)LDL;    very mildly;    mildly and moderately oxidised low-density lipoprotein;    oxNEFA;    oxidised non-esterified fatty acid;    oxPC;    oxidised phosphatidylcholine;    PBS;    phosphate-buffered saline;    PC;    phosphatidylcholine;    PFB;    Pefabloc;    PPAR;    peroxisome proliferator-activated receptor;    PUFA;    polyunsaturated fatty acid;    REM;    relative electrophoretic mobility;    SMC;    smooth muscle cells;    TBARS;    thiobarbituric acid-reactive substances;   

DOI  :  10.1016/S0014-5793(03)01007-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 A₂ (by SB222657) diminished death induction in HMM by both oxLDL types. Peroxisome proliferator-activated receptor γ (PPARγ) antagonist (GW9662) and agonist (ciglitazone) experiments suggested that non-hydrolysed, oxidised phospholipids in oxLDL activate PPARγ as a cellular defence mechanism. These results may be relevant to LDL oxidation within atherosclerotic plaques and may suggest strategies for combating atherosclerosis progression.

【 授权许可】

Unknown