The antioxidant paradox

While the oxidation of LDL by several oxidative enzymes is believed to be a key component driving the retention of mmLDL, foam cell development, and the progression of plaque, the levels of extracellular antioxidants have been found to be quite high within atheroma and approach those of normal human plasma. LDL contains significant quantities of a-tocopherol (vitamin E), a phenolic antioxidant that helps protect LDL from one-electron radical oxidation processes, and does not appear to be depleted in isolated oxLDL. Thus, LDL lipid peroxides and apoB protein oxidation products form even in the presence of a-tocopherol. These and other data challenge the conventional thinking about the importance of modified and oxidized LDL particles in the lipid retention process.22 Alternatively, many of the key oxidation processes that contribute to LDL oxidation may be derived from two-electron oxidations, for which radical scavengers such as a-tocopherol offer no protection.

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