Oxidized HDL

Bergt, Constanze; Oram, John F.; Heinecke, Jay W.

doi:10.1161/01.atv.0000090570.99836.9c

Cited by 26 publications

(10 citation statements)

References 30 publications

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“…In an accompanying editorial, Bergt, Oram, and Heinecke (112) suggested that cross-linked heterodimers of apoA-I and apoA-II in tyrosylated HDL may be responsible for its enhanced ability to remove cholesterol from lipidladen cells (113). These authors (112) speculated that heterodimers may act more like lipid-free apolipoproteins, perhaps because of conformational changes in apoA-I that expose more amphipathic ␣ -helices to ABCA1.…”

Section: Figurementioning

confidence: 99%

“…These authors (112) speculated that heterodimers may act more like lipid-free apolipoproteins, perhaps because of conformational changes in apoA-I that expose more amphipathic ␣ -helices to ABCA1. They also noted that apoA-I mimetic peptides synthesized from d -amino acids appear to retard atherogenesis in hypercholesterolemic mice without affecting HDL levels and that in vitro studies have suggested that this effect is mediated in part by inhibition of LDL oxidation (87).…”

Section: Figurementioning

confidence: 99%

“…They also noted that apoA-I mimetic peptides synthesized from d -amino acids appear to retard atherogenesis in hypercholesterolemic mice without affecting HDL levels and that in vitro studies have suggested that this effect is mediated in part by inhibition of LDL oxidation (87). Bergt, Oram, and Heinecke (112) suggested the possibility that such apoA-I mimetic peptides (87) might also promote reverse cholesterol transport, but this had not been investigated. Additionally, they commented that HDL appears to be the major carrier of lipid hydroperoxides in the plasma and may transport oxidized cholesteryl esters to the liver for excretion (114).…”

Section: Figurementioning

confidence: 99%

“…Additionally, they commented that HDL appears to be the major carrier of lipid hydroperoxides in the plasma and may transport oxidized cholesteryl esters to the liver for excretion (114). They concluded that HDL might also decrease the risk of atherosclerosis by altering the structures or metabolic fates of oxidized lipids that would otherwise exert atherogenic effects (112). (120), and fractions containing HDL and LDL were assayed for LOOH as described (119,120).…”

Section: Figurementioning

confidence: 99%

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Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL

Navab

Ananthramaiah

Reddy

et al. 2004

Journal of Lipid Research

629

436

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For more than two decades, there has been continuing evidence of lipid oxidation playing a central role in atherogenesis. The oxidation hypothesis of atherogenesis has evolved to focus on specific proinflammatory oxidized phospholipids that result from the oxidation of LDL phospholipids containing arachidonic acid and that are recognized by the innate immune system in animals and humans. These oxidized phospholipids are largely generated by potent oxidants produced by the lipoxygenase and myeloperoxidase pathways. The failure of antioxidant vitamins to influence clinical outcomes may have many explanations, including the inability of vitamin E to prevent the formation of these oxidized phospholipids and other lipid oxidation products of the myeloperoxidase pathway. Preliminary data suggest that the oxidation hypothesis of atherogenesis and the reverse cholesterol transport hypothesis of atherogenesis may have a common biological basis. The levels of specific oxidized lipids in plasma and lipoproteins, the levels of antibodies to these lipids, and the inflammatory/antiinflammatory properties of HDL may be useful markers of susceptibility to atherogenesis. Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides may both promote a reduction in oxidized lipids and enhance reverse cholesterol transport and therefore may have therapeutic potential. (1) reported that the oxidation of LDL was injurious to artery wall cells and suggested that LDL oxidation may be important in atherogenesis. They also demonstrated that HDL inhibited the LDL-induced cytotoxicity (1). Over the ensuing two decades, this group elucidated the basis for these observations and established the important role of oxidized cholesterol products, especially cholesterol hydroperoxides (2). THE SEARCH FOR MECHANISMS OF LDL-INDUCEDFOAM CELL FORMATION Also in 1979, Goldstein et al. (3) reported that acetylated LDL but not native LDL was taken up by "scavenger receptors" instead of the LDL receptor, resulting in cholesteryl ester accumulation in macrophages characteristic of foam cells. Because acetylation was not known to occur, after the publication of this seminal paper there was a search for physiological ligands that would explain foam cell formation. Fogelman et al. (4) soon reported that malondialdehyde, an obligate product of the oxidation of arachidonic acid by the lipoxygenase pathways, could cause Schiff-base formation with the epsilon amino groups of apolipoprotein B (apoB) lysines in LDL. The altered lipoprotein was recognized by macrophage scavenger receptors, resulting in cholesteryl ester accumulation characteristic of foam cells. The next year, Steinberg and colleagues (5) demonstrated that cultured endothelial

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL

Navab

Ananthramaiah

Reddy

et al. 2004

Journal of Lipid Research

629

436

View full text Add to dashboard Cite

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“…4-10 At the same time, failure of antioxidants such as vitamin E to protect against atherosclerosis in clinical trials, together with growing evidence that the anti-atherogenic action of the lipid-lowering drug probucol is not related to its antioxidant effects 11 and the notion that such cardioprotective activities as exercise or red wine consumption are pro-oxidant, suggest that not all forms of oxidized lipoproteins are atherogenic. 9,12 Although the central role of LDL oxidation in atherogenesis is widely accepted 9 , the role of HDL oxidation remains contested. Oxidation is generally thought to impair atheroprotective functions of HDL (13 -18 and references therein).…”

Section: Introductionmentioning

confidence: 99%

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein In Vitro

Gao

Jayaraman

Gursky

2008

Journal of Molecular Biology

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SUMMARYHigh-density lipoproteins (HDL) prevent atherosclerosis by removing cholesterol from macrophages and by exerting anti-oxidant and anti-inflammatory effects. Oxidation is thought to impair HDL functions, yet certain oxidative modifications may be advantageous; thus, mild oxidation reportedly enhances cell cholesterol uptake by HDL whereas extensive oxidation impairs it. To elucidate the underlying energetic and structural basis, we analyzed the effects of copper and hypochlorite (that preferentially oxidize lipids and proteins, respectively) on thermal stability of plasma spherical HDL. Circular dichroism, light scattering, calorimetry, gel electrophoresis and electron microscopy showed that mild oxidation destabilizes HDL and accelerates protein dissociation and lipoprotein fusion, while extensive oxidation inhibits these reactions; this inhibition correlates with massive protein cross-linking and lipolysis. We propose that mild oxidation lowers kinetic barriers for HDL remodeling due to diminished apolipoprotein affinity for lipids resulting from oxidation of methionine and aromatic residues in apolipoproteins A-I and A-II followed by protein cross-linking into dimers and/or trimers. In contrast, advanced oxidation inhibits protein dissociation and HDL fusion due to lipid re-distribution from core to surface upon lipolysis and to massive protein crosslinking. Our results help reconcile the apparent controversy in the studies of oxidized HDL and suggest that mild oxidation may benefit HDL functions.

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Preparation of LDL, Oxidation, Methods of Detection, and Applications in Atherosclerosis Research

Narasimhulu

Parthasarathy

2022

Methods in Molecular Biology

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Oxidized HDL

Cited by 26 publications

References 30 publications

Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL

Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein In Vitro

Preparation of LDL, Oxidation, Methods of Detection, and Applications in Atherosclerosis Research

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