Online citations, reference lists, and bibliographies.
← Back to Search

Mildly Oxidized LDL Particle Subspecies Are Distinct In Their Capacity To Induce Apoptosis In Endothelial Cells: Role Of Lipid Hydroperoxides

A. Kontush, L. Chancharme, I. Escargueil-Blanc, P. Thérond, R. Salvayre, A. Négre-Salvayre, M. Chapman
Published 2003 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
The risk of atherosclerosis is intimately related to the heterogeneity of low‐density lipoprotein (LDL) particles. The potential relationship between oxidative modification of distinct LDL subspecies and induction of apoptosis in arterial wall cells is indeterminate. The capacity of light LDL3 versus dense LDL5 to induce cytotoxicity in endothelial cells as a function of the degree of copper‐mediated oxidation was compared. Mildly oxidized LDL3 (oxLDL3) exerted potent cytotoxicity, which was intimately related to both the degree of oxidation and the oxLDL3 concentration based on either cholesterol content or particle number. In contrast, dense LDL5 particles exerted a minor effect on cell viability. Cells incubated with oxLDL3 exhibited apoptotic features, with cytoplasmic condensation, cell or nuclear fragmentation, and accumulation of DNA fragments. OxLDL3‐induced apoptosis involved cytoplasmic release of cytochrome c, with a concomitant increase in caspase‐3‐like protease activity. OxLDL3 particles were uniquely distinct from oxLDL5 particles in their elevated content of lipid hydroperoxides. Hydroperoxide removal by NaBH4 markedly reduced oxLDL3‐induced cytotoxicity, leading to an increase in cell viability. Lipid hydroperoxide content of oxidatively modified LDL subclasses is therefore a major determinant of the induction of apoptosis in endothelial cells. These data are highly relevant to atherogenic hypercholesterolemia, in which the LDL phenotype is dominated by elevated concentrations of light LDL3.
This paper references
10.1074/JBC.M011731200
Inhibition of Oxidized Low-density Lipoprotein-induced Apoptosis in Endothelial Cells by Nitric Oxide
S. Kotamraju (2001)
A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum.
M. J. Chapman (1981)
10.1016/0003-2697(88)90369-7
Evaluation of an isoluminol chemiluminescence assay for the detection of hydroperoxides in human blood plasma.
B. Frei (1988)
10.1096/fasebj.8.13.7926374
Necrosis and apoptosis induced by oxidized low density lipoproteins occur through two calcium‐dependent pathways in lymphoblastoid cells
I. Escargueil-Blanc (1994)
10.1097/00041433-199410000-00005
Heterogeneity of plasma low‐density lipoproteins and atherosclerosis risk
R. Krauss (1994)
Use of the tetrazolium assay in measuring the response of human tumor cells to ionizing radiation.
P. Price (1990)
10.1016/0021-9150(79)90166-7
LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.
J. Hessler (1979)
10.1161/01.CIR.101.21.2450
Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques.
O. Tricot (2000)
10.1161/01.ATV.19.10.2387
Vitamin C protects human vascular smooth muscle cells against apoptosis induced by moderately oxidized LDL containing high levels of lipid hydroperoxides.
R. Siow (1999)
10.1161/01.ATV.21.4.594
Measurement of Copper-Binding Sites on Low Density Lipoprotein
A. Roland (2001)
10.1016/0009-3084(87)90071-5
Lipid peroxides and human diseases.
K. Yagi (1987)
10.1016/s0021-9258(18)61395-x
Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products.
U. Steinbrecher (1987)
10.1172/JCI3531
Oxidized LDL activates fas-mediated endothelial cell apoptosis.
M. Sata (1998)
10.1161/01.CIR.95.7.1760
Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases. A mechanistic clue to the 'response to injury' hypothesis.
S. Dimmeler (1997)
10.1096/fj.99-0986com
Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells
C. Napoli (2000)
10.1016/S0009-3084(97)00038-8
Mechanisms of lipid peroxidation in human blood plasma: a kinetic approach.
B. Karten (1997)
10.1161/01.ATV.17.10.2158
HDL and ApoA prevent cell death of endothelial cells induced by oxidized LDL.
I. Suc (1997)
10.1016/S0021-9150(99)00170-7
Oxidized-LDL induce apoptosis in HUVEC but not in the endothelial cell line EA.hy 926.
C. Claise (1999)
10.1016/S0076-6879(94)33053-0
Rapid isolation of lipoproteins and assessment of their peroxidation by high-performance liquid chromatography postcolumn chemiluminescence.
W. Sattler (1994)
10.1006/BBRC.1996.0907
Oxidized LDL induces apoptosis in cultured smooth muscle cells: a possible role for 7-ketocholesterol.
E. Nishio (1996)
10.1096/fasebj.13.3.485
Bcl‐2 alters the balance between apoptosis and necrosis, but does not prevent cell death induced by oxidized low density lipoproteins
O. Meilhac (1999)
10.1161/01.ATV.15.8.1043
Predominance of large LDL and reduced HDL2 cholesterol in normolipidemic men with coronary artery disease.
H. Campos (1995)
Lipid hydroperoxide generation, turnover, and effector action in biological systems.
A. Girotti (1998)
10.4324/9780203304815_CHAPTER_4
Atherogenicity of Low-density Lipoproteins: Mechanisms
M. Chapman (1999)
10.1016/0005-2760(90)90124-G
Ultraviolet-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. II. Uptake and cytotoxicity of ultraviolet-treated LDL on lymphoid cell lines.
A. Negre-Salvayre (1990)
10.1016/0165-6147(89)90027-8
Mechanisms of cell death.
A. Boobis (1989)
10.1096/fasebj.14.3.532
Oxidized LDLs alter the activity of the ubiquitin‐proteasome pathway: potential role in oxidized LDL‐induced apoptosis
O. Vieira (2000)
Bcl2 alters the balance between apoptosis and necrosis, but does not prevent cell death induced by oxidized low density lipoproteins
O. Meilhac (1999)
10.1161/01.ATV.17.2.331
Oxidized LDLs induce massive apoptosis of cultured human endothelial cells through a calcium-dependent pathway. Prevention by aurintricarboxylic acid.
I. Escargueil-Blanc (1997)
10.1097/00041433-199808000-00009
Is oxidized low-density lipoprotein present in vivo?
S. Ylä-Herttuala (1998)
Further resolution of the low density lipoprotein spectrum in normal human plasma: physicochemical characteristics of discrete subspecies separated by density gradient ultracentrifugation.
M. Chapman (1988)
10.1161/01.ATV.19.3.810
Cholesteryl ester hydroperoxide lability is a key feature of the oxidative susceptibility of small, dense LDL.
L. Chancharme (1999)
10.1016/0021-9150(88)90138-4
Further resolution and comparison of the heterogeneity of plasma low-density lipoproteins in human hyperlipoproteinemias: type III hyperlipoproteinemia, hypertriglyceridemia and familial hypercholesterolemia.
G. Luc (1988)
10.1161/01.CIR.101.8.841
Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes.
Z. Mallat (2000)
LDL particle subclasses in hypercholesterolemia. Molecular determinants of reduced lipid hydroperoxide stability.
L. Chancharme (2002)
Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability.
S. Björkerud (1996)
Peroxisome proliferator-activated receptor activators inhibit thrombininduced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway
P. Delerive (1999)
10.1161/01.ATV.17.10.2225
DNA fragmentation and ultrastructural changes of degenerating cells in atherosclerotic lesions and smooth muscle cells exposed to oxidized LDL in vitro.
S. Jovinge (1997)
10.1161/01.CIR.99.3.348
Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity.
Z. Mallat (1999)
10.1161/01.RES.85.5.394
Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway.
P. Delerive (1999)
10.1016/0891-5849(95)02173-6
The role of oxidized lipoproteins in atherogenesis.
J. Berliner (1996)
10.1172/JCI115261
Minimally modified low density lipoprotein is biologically active in vivo in mice.
F. Liao (1991)
10.1096/fasebj.3.7.2497041
Calcium‐activated DNA fragmentation kills immature thymocytes
D. McConkey (1989)
Evidence for apoptosis in human atherogenesis and in a rat vascular injury model.
D. K. Han (1995)
10.1161/01.ATV.17.12.3469
Endothelial cells prevent accumulation of lipid hydroperoxides in low-density lipoprotein.
D. M. Smalley (1997)
Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme.
Y. Geng (1995)
Oxidized low density lipoproteins induce apoptosis in PHA-activated peripheral blood mononuclear cells and in the Jurkat T-cell line.
J. Alcouffe (1999)
Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor.
F. Nigon (1991)
Apolipoprotein B100 conformation and particle surface charge in human LDL subspecies: implication for LDL receptor
S. Lund-Katz (1998)
10.1161/01.ATV.16.3.416
Contrary effects of lightly and strongly oxidized LDL with potent promotion of growth versus apoptosis on arterial smooth muscle cells, macrophages, and fibroblasts.
B. Björkerud (1996)
10.1073/PNAS.86.4.1372
Low density lipoprotein undergoes oxidative modification in vivo.
W. Palinski (1989)
10.1016/0021-9150(96)05842-X
Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans.
V. Anber (1996)
10.1021/BI980828M
Apolipoprotein B-100 conformation and particle surface charge in human LDL subspecies: implication for LDL receptor interaction.
S. Lund-Katz (1998)
10.1016/S0021-9150(00)00453-6
Lysophosphatidylcholine induces apoptotic and non-apoptotic death in vascular smooth muscle cells: in comparison with oxidized LDL.
C. Hsieh (2000)
10.1161/01.CIR.95.1.69
Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.
B. Lamarche (1997)



This paper is referenced by
Oxidative Stress Small , Dense HDL Particles Exert Potent Protection of Atherogenic LDL Against
S. Chantepie (2003)
10.1170/T641
Oxidation of hemoglobin by lipid hydroperoxide associated with low-density lipoprotein (LDL) and increased cytotoxic effect by LDL oxidation in heme oxygenase-1 (HO-1) deficiency.
E. Nagy (2005)
10.1159/000178151
Modulation of Endothelium and Endothelial Progenitor Cell Function by Low-Density Lipoproteins: Implication for Vascular Repair, Angiogenesis and Vasculogenesis
C. Rodríguez (2009)
10.1016/j.micron.2014.08.002
Distribution of selected elements in calcific human aortic valves studied by microscopy combined with SR-μXRF: influence of lipids on progression of calcification.
G. Lis (2014)
10.1007/s12031-012-9781-x
Vasoactive Intestinal Peptide Enhances Striatal Plasticity and Prevents Dopaminergic Cell Loss in Parkinsonian Rats
OrhanTansel Korkmaz (2012)
The role of low-density lipoprotein modification by mpo-derived oxidants in atherosclerosis
Fahd Ismael (2014)
Atherosclerosis: cell biology and lipoproteins Oxidizedphospholipids inatherosclerosis Related review: Oxidized phospholipids as modulators of inflammation in atherosclerosis
Pp (2003)
10.11606/D.89.2012.TDE-11122013-115131
Influência da obesidade em adolescentes sobre a atividade da paraoxonase (PON1) e o tamanho da Lipoproteína de Alta Densidade (HDL)
Claudia Assef Sanibal (2012)
10.1086/498617
Chlamydia pneumoniae alters mildly oxidized low-density lipoprotein-induced cell death in human endothelial cells, leading to necrosis rather than apoptosis.
D. Nazzal (2006)
10.1161/01.ATV.0000071350.78872.C4
Isolation, Characterization, and Functional Assessment of Oxidatively Modified Subfractions of Circulating Low-Density Lipoproteins
C. Yang (2003)
10.1097/00041433-200310000-00007
Apoptotic cell death in atherosclerosis
T. Littlewood (2003)
Dysfunctional HDL-cholesterol: a potential link between high levels of HDL-cholesterol and cardiovascular disease?
Peta Taylor (2013)
Hyperalphalipoproteinemia : Relevance of Enzymatic and Physicochemical Properties Antioxidative Activity of HDL Particle Subspecies Is Impaired in
E. Faria (2004)
10.1111/j.1582-4934.2009.00713.x
Small, dense HDL 3 particles attenuate apoptosis in endothelial cells: pivotal role of apolipoprotein A-I
Juliana A de Souza (2010)
10.1016/j.biochi.2015.12.014
Oxidative theory of atherosclerosis and antioxidants.
R. Salvayre (2016)
10.1016/j.autneu.2011.08.008
Chemical sympathectomy induces arterial accumulation of native and oxidized LDL in hypercholesterolemic rats
Rafik Hachani (2012)
10.1161/01.ATV.0000118276.87061.00
Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties
A. Kontush (2004)
10.3892/IJMM_00000078
Lipid peroxides induce early onset of catagen phase in murine hair cycles.
A. Naito (2008)
EFFETS DES LIPOPROTÉINES DE FAIBLE DENSITÉ OXYDÉES SUR LES CELLULES OSTÉOBLASTIQUES
D'epartement de Chimie (2008)
10.1016/J.ATHEROSCLEROSIS.2007.08.009
Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity.
Juliana A de Souza (2008)
10.1201/9781420037883.CH2
Apoptosis and Plaque Vulnerability
M. Bennett (2004)
10.1254/JPHS.FP0070385
p38 mitogen-activated protein kinase mediates sidestream cigarette smoke-induced endothelial permeability.
B. Low (2007)
10.1161/01.ATV.0000091338.93223.E8
Small, Dense HDL Particles Exert Potent Protection of Atherogenic LDL Against Oxidative Stress
A. Kontush (2003)
10.1007/s00228-005-0008-8
Nitric oxide and endothelial cell aging
J. Haendeler (2005)
10.1016/J.ATHEROSCLEROSIS.2005.03.029
High-density lipoprotein antagonizes oxidized low-density lipoprotein by suppressing oxygen free-radical formation and preserving nitric oxide bioactivity.
C. Lee (2005)
10.1016/j.peptides.2004.12.019
Brain mast cells and therapeutic potential of vasoactive intestinal peptide in a Parkinson's disease model in rats: Brain microdialysis, behavior, and microscopy
N. Tunçel (2005)
Subfractions of Circulating Low-Density Lipoproteins Isolation , Characterization , and Functional Assessment of Oxidatively Modified
C. Yang (2003)
10.4149/GPB_2015028
Pleiotropic protective roles of melatonin against aluminium-induced toxicity in rats.
M. S. Allagui (2015)
ANTI-ATHEROGENIC FUNCTIONS OF HIGH DENSITY LIPOPROTEINS
W. Ali (2007)
The standardized Ginkgo biloba extract Egb-761 protects vascular endothelium exposed to oxidized low density lipoproteins.
S. Pierre (2008)
10.1016/J.MRFMMM.2006.12.009
Genetic and molecular mechanisms of chemical atherogenesis.
K. Ramos (2007)
Semantic Scholar Logo Some data provided by SemanticScholar