Monocyte superoxide production is inversely related to normal content of α-tocopherol in low-density lipoprotein Original Research Article

Vitamin E (α-tocopherol) is a potent peroxyl radical scavenger. According to the oxidative theory of atherosclerosis, it prevents oxidation of low-density lipoprotein (LDL) and thereby lowers the risk of cardiovascular disease. It also mediates cell actions, and specifically decreases monocyte superoxide anion-production (O2radical dot--production), which is involved in LDL oxidation. We investigated whether α-tocopherol-containing LDL decreases this production in a manner dependent on the LDL α-tocopherol content (the α-tocopherol/apoB molar ratio) in human, phorbol ester-stimulated, adherent monocytes. We found that O2radical dot--production was inhibited by native LDL (n-LDL) in a manner highly sensitive to the increasing α-tocopherol content (range 4.5–8). In addition: (1) inhibition was greater when α-tocopherol was associated to acetylated LDL (ac-LDL), the maximal percentage of inhibition being 80% as opposed to 35% for n-LDL; (2) the α-tocopherol overloading of either form of LDL did not produce further inhibition; (3) the free form of α-tocopherol produced lower inhibition compared with the lipoprotein-associated forms; (4) inhibition was not related to the cell content of α-tocopherol. We propose that the cell targeting of α-tocopherol is crucial to the inhibition of monocyte O2radical dot−-production, and thus that the role of normal LDL-α-tocopherol contents (range 6–8) in the prevention of atherogenic processes needs to be reexamined.