Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger receptor expression in cultured aortic smooth muscle cells

Background-Vitamin E is well known as an antioxidant, and numerous studies suggest that it has a preventive role in atherosclerosis. although the mech anism of action still remains unclear. Methods and Results-The original aim of this study was to establish whether alpha-tocopherol (the most active form of vitamin E) acts at the earliest events on the cascade of atherosclerosis progression, that of oxidized LDL (oxLDL) uptake and foam-cell formation. We show here that the CD36 scavenge r receptor (a specific receptor for oxLDL) is expressed in cultured human a ortic smooth muscle cells (SMCs). Treatment of SMCs and HL-60 macrophages w ith alpha-tocopherol (50 mu mol/L, a physiological concentration) downregul ates CD36 expression by reducing its promoter activity. Furthermore, we fin d that alpha-tocopherol treatment of SMCs leads to a reduction of oxLDL upt ake. Conclusions-This study indicates that CD36 is expressed in cultured human S MCs. In these cells, CD36 transports oxLDL into the cytosol. alpha-Tocopher ol inhibits oxLDL uptake by a mechanism involving downregulation of CD36 mR NA and protein expression. Therefore, the beneficial effect of alpha-tocoph erol against atherosclerosis can be explained, at least in part, by its eff ect of lowering the uptake of oxidized lipoproteins, with consequent reduct ion of foam cell formation.