LDLs damaged

Dinis, T. C., C. L. Santosa, and L. M. Almeida. 2002. The apoprotein is the preferential target for peroxynitrite-induced LDL damage protection by dietary phenolic acids. Free Radical Res. 36 531-543. 

It is unlikely that the damaging effects of ox-LDL are relevant only to the walls of blood vessels and there is no reason to suppose they are confined to one disease. The initial histopathologjcal sign of coronary heart disease is the appearance of the fetty streak on the luminal surfece of arteries. Fatty streaks are composed of aggregated macrophages that have taken up ox-LDL via the scavenger receptor. Recently, we have detected such foam cells in the rheumatoid synovium (Section 5.5). 

Glycosylation of LDL may involve free-radical reactions and itself lead to oxidative damage (Steinbrecher et al., 1984 Esterbauer etal., 1992). However, it appears that glycated LDL is poorly recognized by the classical LDL receptor, but is preferentially recognized by a high-... 

In 1998, Schlotte et al. [259] showed that uric acid inhibited LDL oxidation. However, subsequent studies showed that in the case of copper-initiated LDL oxidation uric acid behaves itself as prooxidant [260,261]. It has been suggested that in this case uric acid enhances LDL oxidation by the reduction of cupric into cuprous ions and that the prooxidant effect of uric acid may be prevented by ascorbate. On the other hand, urate radicals formed during the interaction of uric acid with peroxyl radicals are able to react with other compounds, for example, flavonoids [262], and by that participate in the propagation of free radical damaging reactions. In addition to the inhibition of oxygen radical-mediated processes, uric acid is an effective scavenger of peroxynitrite [263]. 

High antioxidative activity carvedilol has been shown in isolated rat heart mitochondria [297] and in the protection against myocardial injury in postischemic rat hearts [281]. Carvedilol also preserved tissue GSL content and diminished peroxynitrite-induced tissue injury in hypercholesterolemic rabbits [298]. Habon et al. [299] showed that carvedilol significantly decreased the ischemia-reperfusion-stimulated free radical formation and lipid peroxidation in rat hearts. Very small I50 values have been obtained for the metabolite of carvedilol SB 211475 in the iron-ascorbate-initiated lipid peroxidation of brain homogenate (0.28 pmol D1), mouse macrophage-stimulated LDL oxidation (0.043 pmol I 1), the hydroxyl-initiated lipid peroxidation of bovine pulmonary artery endothelial cells (0.15 pmol U1), the cell damage measured by LDL release (0.16 pmol l-1), and the promotion of cell survival (0.13 pmol l-1) [300]. SB 211475 also inhibited superoxide production by PMA-stimulated human neutrophils. 

The antioxidant effect of tamoxifen has also been postulated to underlie some beneficial cardiovascular effect of this and other SERMs. Oxidative damage of LDL plays an important role in the development of atherosclerosis, and it has been postulated that these highly lipophilic molecules stabilize LDL... 

J.D.O Reilly, T.A.B. Sanders and H. Wieseman, Flavonoids protect against oxidative damage to LDL in vitro use in selection of a flavanol rich diet and relevance to LDL oxidation resistance ex vivol Free Radical Res. 33 (2000) 419 -26. 

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