Lipid peroxide and transition metals are required for the toxicity of oxidized low density lipoprotein to cultured endothelial cells

Kuzuya, Masafumi; Naito, Michitaka; Funaki, Chiaki; Hayashi, Toshio; Asai, Kuniya; Kuzuya, Fumio

doi:10.1016/0925-4439(91)90054-d

Cited by 81 publications

(53 citation statements)

References 35 publications

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“…In addition to aldehydes, oxidised LDL contains other cytotoxic components, e.g. lipid hydroperoxides and oxysterols [23,24]. Thus toxicity of oxidised LDL could arise from the combined effect of these and other as yet unidentified cytotoxins.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

et al. 1996

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Section: Discussionmentioning

confidence: 99%

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

et al. 1996

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“…LDL was oxidized by incubating 500 g/mL LDL in 10 mol/L CuSO 4 for 16 hours at 37°C and then dialyzed in PBS containing 0.1 mmol/L EDTA for 24 hours at 4°C, followed by further dialysis against PBS for 24 hours at 4°C to exclude EDTA as previously described. 27,28 Fresh preparations of LDL and Ox-LDL were used for each experiment.…”

Section: Ldl Preparationmentioning

confidence: 99%

“…27 EDTA was removed from the LDL by dialysis against PBS before oxidation or immediately before addition to the cell culture medium for native LDL. LDL was oxidized by incubating 500 g/mL LDL in 10 mol/L CuSO 4 for 16 hours at 37°C and then dialyzed in PBS containing 0.1 mmol/L EDTA for 24 hours at 4°C, followed by further dialysis against PBS for 24 hours at 4°C to exclude EDTA as previously described.…”

Section: Ldl Preparationmentioning

confidence: 99%

Induction of Macrophage VEGF in Response to Oxidized LDL and VEGF Accumulation in Human Atherosclerotic Lesions

Ramos

Kuzuya

Esaki

et al. 1998

ATVB

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134

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Abstract-The interaction between macrophages and oxidatively modified low density lipoprotein (Ox-LDL) appears to play a central role in the development of atherosclerosis, not only through foam cell formation but also via the induction of numerous cytokines and growth factors. The current study demonstrated that Ox-LDL upregulated vascular endothelial growth factor (VEGF) mRNA expression in RAW 264 cells, a monocytic cell line, in a time-and concentration-dependent manner and that Ox-LDL stimulated VEGF protein secretion from the cells. Lysophosphatidylcholine, a component of Ox-LDL, also enhanced VEGF mRNA expression in RAW 264 cells and VEGF secretion from RAW 264 cells, with a maximal effect at a concentration of 10 mol/L lysophosphatidylcholine. Immunohistochemical studies showed that human early atherosclerotic lesions exhibited intense VEGF immunoreactivity in subendothelial macrophage-rich regions of the thickened intima. In atherosclerotic plaques, VEGF staining was also observed in foam cell-rich regions adjacent to the lipid core or the neovascularized basal regions of plaque consisting predominantly of smooth muscle cells. High-power-field observation revealed that VEGF was localized in the extracellular space as well as at the macrophage cell surface. These observations suggest the possible involvement of Ox-LDL in the development of human atherosclerosis through VEGF induction in macrophages. (Arterioscler Thromb

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“…66,67 Column chromatography gives very low estimates of copper binding to LDL. 24,26,30 There is likely to be a problem with this technique, inasmuch as copper ions bind to Sephadex during column chromatography. This can be readily seen by passing LDL-copper complexes through Sephadex G-25 PD-10 columns (Pharmacia Biotech) and eluting with BC and ascorbate after the LDL has emerged and the column has been eluted with several times its bed volume.…”

Section: Discussionmentioning

confidence: 99%

“…This binding occurs, at least in part, to histidine-containing sites on apoB-100, the protein moiety of LDL. 22,23 The number of binding sites reported varies widely over 2 orders of magnitude [22][23][24][25][26][27][28][29][30][31][32][33] (Table).…”

mentioning

confidence: 99%

Measurement of Copper-Binding Sites on Low Density Lipoprotein

Roland

Patterson

Leake

2001

ATVB

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Abstract-Copper is often used to oxidize low density lipoprotein (LDL) in experiments in vitro and is a candidate for oxidizing LDL in atherosclerotic lesions. The binding of copper ions to LDL is usually thought to be a prerequisite for LDL oxidation by copper, although estimates of LDL copper binding vary widely. We have developed and validated an equilibrium dialysis assay in a MOPS-buffered system to measure copper binding to LDL and have found 38.6Ϯ0.7 (meanϮSEM, nϭ25) copper binding sites on LDL. The binding was saturated at a copper concentration of 10 mol/L at LDL concentrations of up to 1 mg protein/mL. Copper-binding capacity increased progressively and markedly when LDL was oxidized to increasing extents. Chemical modification of histidyl and lysyl residues on apolipoprotein B-100 reduced the number of binding sites by 56% and 23%, respectively. As an example of the potential of this method to assess the effects of antioxidants on copper binding to LDL, we have shown that the flavonoids myricetin, quercetin, and catechin (but not epicatechin, kaempferol, or morin), at concentrations equimolar to the copper present (10 mol/L), significantly decreased copper binding to LDL by 82%, 56%, and 20%, respectively.

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Lipid peroxide and transition metals are required for the toxicity of oxidized low density lipoprotein to cultured endothelial cells

Cited by 81 publications

References 35 publications

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte‐macrophages

Induction of Macrophage VEGF in Response to Oxidized LDL and VEGF Accumulation in Human Atherosclerotic Lesions

Measurement of Copper-Binding Sites on Low Density Lipoprotein

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