Macrophages actively accumulate malonyldialdehyde-modified but not enzymatically oxidized low density lipoprotein.
ABSTRACT In this study, we show that low density lipoproteins (LDL) from human blood plasma which was oxidized by animal C-15 lipoxygenase is taken up by cultivated human macrophages with the same effectiveness as with non-oxidized (native) LDL. At the same time malonyldialdehyde-modified LDL is captured by cultivated macrophages very actively. Based on differences in catabolism of LDL with various levels of primary and secondary products of free-radical oxidation, it was offered to discriminate between the oxidized LDL itself (lipohydroperoxide-rich LDL) and the LDL that was chemically modified by free-radical oxidation secondary products of aldehyde nature. In this respect, aldehyde-modified but not oxidized (lipohydroperoxide-containing) LDL is atherogenic.
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ABSTRACT: Excessive uptake of oxidized low density lipoprotein plays a role in the onset of atherosclerosis. Lipid-associated antioxidants, the most abundant of which is tocopherol (vitamin E), are therefore believed to have anti-atherogenic properties. By contrast, hydroperoxides enhance the peroxidation of low density lipoprotein. We demonstrate that none of these compounds markedly affect the maximal rate of oxidation of low density lipoprotein, whereas the lag preceding rapid oxidation is prolonged by tocopherol but shortened by hydroperoxides. The corresponding 'prolongation' and 'shortening' can be compensated by each other in low density lipoprotein preparations enriched with both these compounds. The dependence of the balance between the effects of tocopherol and hydroperoxides on the copper concentration indicates that the antioxidative effect of vitamin E increases with the oxidative stress.FEBS Letters 06/1999; 450(3):186-90. · 3.34 Impact Factor
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ABSTRACT: Glutaraldehyde treatment of (125)I-labeled low density lipoprotein ((125)I-native-LDL) produced a modified LDL ((125)I-glut-LDL) with a molecular weight of 10 x 10(6) or more. Malondialdehyde treatment of (125)I-native-LDL produced a product ((125)I-MDA-LDL) with a molecular weight not appreciably different from that of the original lipoprotein. However, the electrophoretic mobility of MDA-LDL indicated a more negative charge than native-LDL. (125)I-MDA-LDL was degraded by two processes: a high-affinity saturable process with maximal velocity at 10-15 mug of protein per ml and a slower, nonsaturable process. The degradation of (125)I-MDA-LDL was readily inhibited by increasing concentrations of nonradioactive MDA-LDL but was not inhibited by acetylated LDL or native-LDL even at concentrations as high as 1600 mug of protein per ml. After exposure of native-LDL to blood platelet aggregation and release in vitro, 1.73 +/- 0.19 nmol of malondialdehyde per mg of LDL protein was bound to the platelet-modified-LDL. No detectable malondialdehyde was recovered from native-LDL that had been treated identically except that the platelets were omitted from the reaction mixture. After incubation with glut-LDL, MDA-LDL, or platelet-modified-LDL for 3 days, human monocyte-macrophages showed a dramatic increase in cholesteryl ester content whereas the cholesteryl ester content of cells incubated with the same concentration of native-LDL did not. Based on these experiments we propose that modification of native-LDL may be a prerequisite to the accumulation of cholesteryl esters within the cells of the atherosclerotic reaction. We further hypothesize that one modification of LDL in vivo may result from malondialdehyde which is released from blood platelets or is produced by lipid peroxidation at the site of arterial injury.Proceedings of the National Academy of Sciences 05/1980; 77(4):2214-8. · 9.81 Impact Factor
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ABSTRACT: Lipoprotein oxidation induced in vitro in whole plasma is expected to be a more relevant model of the lipoprotein oxidation in the arterial wall than the in vitro oxidation of single isolated lipoproteins, e.g., low density lipoprotein (LDL). However, it is unclear, whether the oxidizability of whole plasma may serve as an adequate measure of the oxidizability of plasma lipoproteins. We measured the oxidizability of whole plasma diluted 150-fold as an absorbance increase at 234 nm known to reflect the level of conjugated dienes in the samples. Plasma oxidation was induced by Cu(II), 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH), lipoxygenase or myeloperoxidase+H2O2. Oxidizability of human plasma measured in the presence of Cu(II) was found to correlate with the oxidizability of LDL measured in the common Cu(II)-based LDL oxidation assay. The plasma oxidizability also correlated positively with plasma oxidizable fatty acid and negatively with plasma antioxidant content. Supplementation of human plasma with different antioxidants (albumin, urate, ascorbate, bilirubin, alpha-tocopherol and ubiquinol-10) in vitro decreased its oxidizability. Supplementation of Watanabe heritable hyperlipidaemic rabbits with different antioxidants (vitamin E, ubiquinone-10, probucol, carvedilol) in vivo lowered the oxidizability of rabbit plasma in comparison with rabbits fed standard diet. When plasma from hyperlipidaemic patients with or without coronary heart disease and from age-matched healthy controls was studied, the plasma oxidizability was found to be highest in the patients with coronary heart disease and lowest in the controls. Taken together, these data indicate that the plasma oxidation assay (i) provides information similar to that obtained using the common LDL oxidation assay, (ii) upgrades the latter, taking into account the effect of hydrophilic antioxidants on lipoprotein oxidation and characterizing the oxidizability of all plasma lipoproteins, and (iii) offers important practical advantages, such as fast and simple sample processing, low amount of plasma required and avoidance of artefactual oxidation during lipoprotein isolation. We propose the measurement of plasma oxidizability at 234 nm as an adequate practical index of the oxidizability of plasma lipoproteins.BioFactors 02/1997; 6(2):99-109. · 3.00 Impact Factor