(Circulation. 2000;102:82.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
From the Institute of Biochemistry and Molecular Biology, University of Bern, Bern, Switzerland. Drs Ricciarelli and Zingg contributed equally to this work.
Correspondence to A. Azzi, MD, Institut für Biochemie und Molekularbiologie, Universität Bern, Bühlstrasse 28, Bern 3012, Switzerland. E-mail angelo.azzi{at}mci.unibe.ch
BackgroundVitamin 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.
Methods and ResultsThe original aim of this study was to
establish whether
-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
-tocopherol (50
µmol/L, a physiological concentration)
downregulates CD36 expression by reducing its promoter activity.
Furthermore, we find that
-tocopherol treatment of SMCs
leads to a reduction of oxLDL uptake.
ConclusionsThis study indicates that CD36 is expressed in
cultured human SMCs. In these cells, CD36 transports oxLDL into the
cytosol.
-Tocopherol inhibits oxLDL uptake by a
mechanism involving downregulation of CD36 mRNA and protein expression.
Therefore, the beneficial effect of
-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.
Key Words: tocopherol receptors lipoproteins atherosclerosis
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