Inhibition of LDL oxidation by antioxidants.
Low density lipoprotein (LDL) consists of about 3000 fatty acids (50% polyunsaturated) and a single molecule apolipoprotein B (500 kDa). The endogenous antioxidants of LDL consist mainly of tocopherols and few carotenoids, which protect the PUFAS against oxidation. That native LDL contains traces of oxidation products has not been proved yet. Oxidatively modified LDL (oLDL) exhibits cytotoxic and chemotactic activities, furthermore it leads to foam cell formation, a critical step in atherogenesis. The oxidation of LDL is a free radical process and leads to various aldehydic products. The oxidation of LDL is initiated by cells as well as by transition metals like Cu2+. In both cases the oxidation goes through three consecutive phases. The lag-phase is characterized by minimal degradation of PUFAs but a loss of the antioxidants. Thereafter the PUFAs are oxidized to lipid hydroperoxides, which are only intermediates (propagation-phase). These intermediates will decompose to aldehydic products, accompanied by several additional changes in the LDL particle (decomposition-phase). For increased macrophage uptake oLDL must reach the late decomposition-phase; the presence of lipid hydroperoxides in LDL is not sufficient. It is suggested that binding of aldehydes to free amino groups of Apo B is the reason for macrophage uptake. This is supported by the finding that antibodies against aldehyde-modified LDL are able to recognize oxidized LDL in atherosclerotic lesions. Antioxidants like alpha-tocopherol are able to protect LDL against oxidation. The duration of the lag-phase shows a linear relationship with the content of alpha-tocopherol in LDL. Yet the efficiency of alpha-tocopherol to protect LDL shows strong individual variation.
Esterbauer
H
H
Institute of Biochemistry, University of Graz, Austria.
Waeg
G
G
Puhl
H
H
Dieber-Rotheneder
M
M
Tatzber
F
F
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002338:Carotenoids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D008077:Lipoproteins, LDL; D014810:Vitamin E; D002338:Carotenoids