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

Keri L H Carpenter; Iain R Challis; Mark J Arends

doi:10.1016/S0014-5793(03)01007-X

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

Keri L H Carpenter, Iain R Challis, Mark J Arends

School of Population Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	145-50
Number of pages	6
Journal	FEBS Letters
Volume	553
Issue number	1-2
DOIs	https://doi.org/10.1016/S0014-5793(03)01007-X
Publication status	Published - 9 Oct 2003

Keywords / Materials (for Non-textual outputs)

1-Alkyl-2-acetylglycerophosphocholine Esterase
Apoptosis
Humans
Lipid Peroxidation
Lipoproteins, LDL
Macrophages
Oxidation-Reduction
Phospholipases A
Phospholipases A2
Receptors, Cytoplasmic and Nuclear
Time Factors
Transcription Factors

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10.1016/S0014-5793(03)01007-X

Mildly oxidised LDL induces more macrophage death than moderately oxidis
copyright 2003 Federation of European Biochemical Societies. Open access article
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http://www.sciencedirect.com/science/article/pii/S001457930301007X

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

abstract = "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.",

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author = "Carpenter, \{Keri L H\} and Challis, \{Iain R\} and Arends, \{Mark J\}",

year = "2003",

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doi = "10.1016/S0014-5793(03)01007-X",

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T1 - Mildly oxidised LDL induces more macrophage death than moderately oxidised LDL

T2 - roles of peroxidation, lipoprotein-associated phospholipase A2 and PPARgamma

AU - Carpenter, Keri L H

AU - Challis, Iain R

AU - Arends, Mark J

PY - 2003/10/9

Y1 - 2003/10/9

N2 - 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.

AB - 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.

KW - 1-Alkyl-2-acetylglycerophosphocholine Esterase

KW - Apoptosis

KW - Humans

KW - Lipid Peroxidation

KW - Lipoproteins, LDL

KW - Macrophages

KW - Oxidation-Reduction

KW - Phospholipases A

KW - Phospholipases A2

KW - Receptors, Cytoplasmic and Nuclear

KW - Time Factors

KW - Transcription Factors

U2 - 10.1016/S0014-5793(03)01007-X

DO - 10.1016/S0014-5793(03)01007-X

M3 - Article

C2 - 14550563

SN - 0014-5793

VL - 553

SP - 145

EP - 150

JO - FEBS Letters

JF - FEBS Letters

IS - 1-2

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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