Effect of α-tocopherol on LDL oxidation and glycation: In vitro and in vivo studies

Much data support a role for both low density lipoprotein (LDL) oxidation and glycation in atherogenesis. While α-tocopherol decreases the oxidative susceptibility of LDL, its role in decreasing LDL glycation is unclear. Hence we tested the effect of α-tocopherol both in vitro and in vivo on LDL oxidation and glycation. LDL was isolated after enrichment of plasma with α-tocopherol. This resulted in a 2-fold increase in α- tocopherol in LDL (AT-LDL). During a 6-day incubation of control LDL (C-LDL) and AT-LDL with 25 mM glucose, there were no significant differences in the degree of glycation on days 1, 3, and 6. Also, apoB advanced glycosylation end product levels were not significantly different between C-LDL and AT- LDL. There was a progressive increase in the susceptibility of LDL to oxidation with increasing LDL glycation as evidenced by reduced lag time of copper-catalyzed LDL oxidation. However, AT-LDL, was more resistant to copper-catalyzed oxidation. Similar findings were observed when the LDLs were incubated with endothelial cells. The data from the α-tocopherol supplementation study confirmed our in vitro findings that α-tocopherol significantly decreases oxidative susceptibility of LDL, but does not affect its glycation. Therefore, while glycation increases LDL oxidative susceptibility, α-tocopherol decreases the oxidation of glycated LDL but not LDL glycation.