A Cytotoxic Electronegative LDL Subfraction Is Present in Human Plasma

Demuth, Karine; Myara, I.; Chappey, B.; Védie, Benoît; Pech-Amsellem, Marie Agnès; Haberland, Margaret E.; Moatti, N.

doi:10.1161/01.atv.16.6.773

Cited by 100 publications

(81 citation statements)

References 54 publications

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“…Although some authors reported that LDL(Ϫ) contained increased oxidation products, 9,18,24 other investigators found no evidence of oxidative modification. 7,8,10 The high activity of PAF-AH in LDL(Ϫ) points to a possible role of this enzyme in the inflammatory effect of LDL(Ϫ). PAF-AH activity generates LPC and short-chain or oxidized NEFA.…”

Section: Discussionmentioning

confidence: 99%

“…6 Electronegative LDL [LDL(Ϫ)] is a subfraction of LDL present in plasma that induces the release of interleukin-8 and monocyte chemotactic protein-1 7,8 and is cytotoxic in cultured human endothelial cells. 9,10 The mechanism by which LDL(Ϫ) induces chemokine release remains unknown, although it could be related to some compositional differences compared with native LDL, with the most remarkable difference being an increased NEFA content in LDL(Ϫ) compared with native LDL. 7,8 The aim of the present work was to study whether the origin of increased NEFA in LDL(Ϫ) could be related to LDLassociated PLA 2 activity.…”

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confidence: 99%

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Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction

et al. 2003

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Background-Electronegative LDL [LDL(Ϫ)], a modified subfraction of LDL present in plasma, induces the release of interleukin-8 and monocyte chemotactic protein-1 from cultured endothelial cells. Methods and Results-We demonstrate that platelet-activating factor acetylhydrolase (PAF-AH) is mainly associated with LDL(Ϫ). LDL(Ϫ) had 5-fold higher PAF-AH activity than the nonelectronegative LDL subfraction [LDL(ϩ)] in both normolipemic and familial hypercholesterolemic subjects. Western blot analysis after SDS-PAGE confirmed these results, because a single band of 44 kDa corresponding to PAF-AH appeared in LDL(Ϫ) but not in LDL(ϩ).Nondenaturing polyacrylamide gradient gel electrophoresis demonstrated that PAF-AH was bound to LDL(Ϫ) regardless of LDL size. In accordance with the above findings, nonesterified fatty acids, a cleavage product of PAF-AH, were increased in LDL(Ϫ) compared with LDL(ϩ). Conclusions-The

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction

et al. 2003

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“…39 However, recent data show that modification of LDL can occur in the blood. [13][14][15][16][17] Furthermore, prolonged LDL circulation times in the blood increase LDL's propensity to oxidation and may lead to LDL modification before it enters the artery wall. 40 Previous work from this laboratory showed that even short exposures to environmental tobacco smoke (4 hours) increased LDL accumulation in the artery wall.…”

Section: Discussionmentioning

confidence: 99%

“…12 Recent studies demonstrate evidence of modification of LDL in the blood. [13][14][15][16][17] Furthermore, a previous study showed increased accumulation and degradation of oxidized LDL (OX-LDL) in the artery wall in vivo. 18 These studies suggest that the reason there is increased accumulation and degradation of OX-LDL is because arterial permeability to undegraded, OX-LDL is greater than arterial permeability to native LDL (N-LDL).…”

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confidence: 99%

Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17β-Estradiol

Gardner

Banka

Roberts

et al. 1999

ATVB

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Abstract-Current research suggests that estrogen may have primary effects on the artery wall. To investigate the mechanisms of female sex hormone actions in the artery wall, we used an isolated, perfused, rat carotid artery model to examine the effects of estradiol on the rates of accumulation of normal (N-LDL) and minimally modified (MM-LDL) low density lipoprotein in ovariectomized rats. N-LDL, MM-LDL, and oxidized LDL (OX-LDL) were fluorescently labeled and perfused into individual arteries. The rate of LDL accumulation was measured by quantitative fluorescence microscopy before and after treatment with estradiol (1 nmol/L, 272 pg/mL). Estradiol had no effect on the rate of Key Words: artery Ⅲ arteriosclerosis Ⅲ LDL Ⅲ estrogen Ⅲ oxidized LDL Ⅲ endothelium Ⅲ permeability A cardinal characteristic of the development of atherosclerosis is the accumulation of LDL within the arterial wall. 1-3 Sites of relative increase in LDL permeability have been identified in normal arteries 4 and can be induced by injury to the endothelium. 5-9 Alternatively, others have reported increased binding and decreased efflux of LDL from the vascular wall, even under conditions where LDL influx was not affected. 10,11 Therefore, LDL accumulation in the artery wall potentially occurs by several mechanisms, perhaps depending on the stage of atheroma formation.A large body of evidence indicates that modification of LDL in the artery wall promotes atherosclerosis. 12 Recent studies demonstrate evidence of modification of LDL in the blood. [13][14][15][16][17] Furthermore, a previous study showed increased accumulation and degradation of oxidized LDL (OX-LDL) in the artery wall in vivo. 18 These studies suggest that the reason there is increased accumulation and degradation of OX-LDL is because arterial permeability to undegraded, OX-LDL is greater than arterial permeability to native LDL (N-LDL). However, the precise mechanism(s) by which modified LDL (MM-LDL) affects LDL flux in the artery wall, such as increases in permeability to LDL, remains incompletely understood.Modification of LDL (eg, oxidation), either in the circulation or the artery wall, could promote atherosclerosis by increasing LDL accumulation in the artery. Also, alteration of constituents of the artery wall, such as proteoglycans, could influence LDL binding to the artery wall. Furthermore, oxidant-mediated injury of endothelial cell membranes could compromise the endothelial layer barrier to macromolecules in arteries. 5 To counteract oxidant stress effects on LDL and/or the artery wall, a number of potential antioxidants have been examined. In particular, some estrogens (eg, 17␤-estradiol) are known to reduce LDL accumulation in the artery wall 19,20 and to be potent antioxidants. [21][22][23] In addition, estrogens may protect endothelial cells from oxidative damage. 21,22 This action would be expected to prevent increased LDL permeation into the artery wall. Furthermore, estradiol has been shown to inhibit LDL oxidation in vivo at supraphysiological 24 and physiolo...

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“…lipid hydroperoxides and oxysterols [8]. It binds with diminished a¤nity to LDL receptors of human skin ¢broblasts and endothelial cells [9] but is a poor ligand for macrophage scavenger receptor [10]. In contrast to nLDL, LDL 3 is cytotoxic to cultured endothelial cells [11].…”

Section: Introductionmentioning

confidence: 99%

Hypochlorite induces the formation of LDL⁻, a potentially atherogenic low density lipoprotein subspecies

et al. 2001

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Oxidation of low density lipoprotein (LDL) induced by hypochlorous acid (HOCl) leading to LDL 3 , a minimally oxidized subspecies of LDL, was investigated. LDL 3 is characterized by its greater electronegativity and oxidative status, and is found in plasma in vivo. Its concentration was found to be elevated under conditions that predispose humans to atherosclerosis. We found that HOCl also converts LDL rapidly to an even more oxidized state, identified as LDL 23 , which is more electronegative than LDL 3 . After milder oxidation for short durations, formation of LDL 3 takes place while less LDL 23 is formed. Under these conditions, addition of methionine not only suppressed further oxidation of LDL but also favored the formation of LDL 3 over LDL 23 , possibly by removing chloramines at lysyl residues of LDL. The presence of lipoprotein-deficient plasma did not prevent HOCl-mediated conversion of LDL to more electronegative species. It is concluded that the HOCl-mediated conversion of LDL into more electronegative species might be physiologically relevant. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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A Cytotoxic Electronegative LDL Subfraction Is Present in Human Plasma

Cited by 100 publications

References 54 publications

Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction

Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction

Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17β-Estradiol

Hypochlorite induces the formation of LDL⁻, a potentially atherogenic low density lipoprotein subspecies

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A Cytotoxic Electronegative LDL Subfraction Is Present in Human Plasma

Cited by 100 publications

References 54 publications

Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction

Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction

Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17β-Estradiol

Hypochlorite induces the formation of LDL−, a potentially atherogenic low density lipoprotein subspecies

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Hypochlorite induces the formation of LDL⁻, a potentially atherogenic low density lipoprotein subspecies