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 mechanism of action still remains unclear.


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 scavenger receptor (a specific receptor for oxLDL) is expressed in cultured human aortic smooth muscle cells (SMCs). Treatment of SMCs and HL-60 macrophages with alpha-tocopherol (50 micromol/L, a physiological concentration) downregulates CD36 expression by reducing its promoter activity. Furthermore, we find that alpha-tocopherol treatment of SMCs leads to a reduction of oxLDL uptake.


CONCLUSIONS
This study indicates that CD36 is expressed in cultured human SMCs. In these cells, CD36 transports oxLDL into the cytosol. alpha-Tocopherol inhibits oxLDL uptake by a mechanism involving downregulation of CD36 mRNA and protein expression. Therefore, the beneficial effect of alpha-tocopherol against atherosclerosis can be explained, at least in part, by its effect of lowering the uptake of oxidized lipoproteins, with consequent reduction of foam cell formation.
Ricciarelli
R
R
Institute of Biochemistry and Molecular Biology, University of Bern, Bern, Switzerland.
Zingg
J M
JM
Azzi
A
A
D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005786:Gene Expression Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection; D014810:Vitamin E / Q000494:pharmacology*
D018955:CD36 Antigens; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D014810:Vitamin E