Based on the oxidation hypothesis high doses of
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
-tocopherol have been advocated to prevent atherosclerosis, but clinical trials failed to demonstrate a benefit. As specific oxylipids activate PPARγ and
LXR![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
, master regulators of lipid metabolism and cholesterol exporters, we hypothesized, that high dose
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
-tocopherol might interfere with reverse cholesterol transport out of the vessel wall. Human THP-1 cells, a foam cell model, were preincubated with
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
-tocopherol or carrier before exposure to oxidized LDL, delipidated HDL or control buffer. Specific mRNAs were quantified by real-time RT-PCR, LXR
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
activation by a reporter gene assay and cellular cholesterol homeostasis by oxLDL and dHDL facilitated uptake and efflux assays.
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
-Tocopherol significantly reduced baseline expression and stimulation by oxLDL of LXR
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
activity, CD36, ABCA1, and ABCG1.
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
-Tocopherol also reversed the suppression of CD36 and ABCA1 by dHDL. Thus
![greek small letter alpha greek small letter alpha](http://www.sciencedirect.com/scidirimg/entities/204e.gif)
-Tocopherol compromises cellular lipid scavenging and channelling of cholesterol into reverse transport out of the vessel wall.