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

Circulation. 2000 Jul 4;102(1):82-7. doi: 10.1161/01.cir.102.1.82.

Abstract

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.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / cytology
  • Arteriosclerosis / metabolism
  • CD36 Antigens / genetics*
  • CD36 Antigens / metabolism
  • Cells, Cultured
  • Flow Cytometry
  • Fluorescent Dyes / pharmacokinetics
  • Gene Expression Regulation / drug effects
  • HL-60 Cells
  • Humans
  • Lipoproteins, LDL / pharmacokinetics*
  • Microscopy, Confocal
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Promoter Regions, Genetic / physiology
  • RNA, Messenger / analysis
  • Transfection
  • Vitamin E / pharmacology*

Substances

  • CD36 Antigens
  • Fluorescent Dyes
  • Lipoproteins, LDL
  • RNA, Messenger
  • oxidized low density lipoprotein
  • Vitamin E