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Prevention of Atherosclerosis by α-Tocopherol in Smooth Muscle Cells by a Mechanism Involving Signal Transduction Modulation

  • Nesrin K. Özer
  • Önder Sirikci
  • Suzan Taha
  • N. Kaya Engin
  • Daniel Boscoboinik
  • Sophie Clément
  • Achim Stocker
  • Angelo Azzi
Chapter
Part of the NATO ASI Series book series (NSSA, volume 296)

Abstract

α-Tocopherol, the biologically most active form of Vitamin E, decreases in a concentration dependent way, proliferation of smooth muscle cells. At the same concentrations (10 – 50 μM) it induces inhibition of protein kinase C activity. Proliferation and protein kinase C inhibition by α-tocopherol, the lack of inhibition by β-tocopherol and the prevention by ß-tocopherol indicate that the mechanism involved is not related to the radical-scavenging properties of these two molecules, which are essentially equal. All-rac-α-tocopherol is less potent than RRR-α-tocopherol on smooth muscle cell proliferation. probucol (10 – 50 μM), a potent lipophilic antioxidant, does not inhibit smooth muscle cell proliferation and protein kinase C activity. In rabbit studies, atherosclerosis was induced by a 2% cholesterol-containing, vitamin E poor-diet. Six different groups of rabbits each were received vitamin E, probucol; probucol plus vitamin E. After 4 weeks, aortas were analysed for protein kinase C activity. Their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol induced atherosclerotic lesions and the induction of protein kinase C activity. Probucol was not effective in preventing both cholesterol induced atherosclerotic lesions and the induction of protein kinase C activity. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as probucol and therefore may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells ex-vivo and cell culture suggest an involvement of signal transduction events on the onset of atherosclerosis. It is at this level that the protective effect of vitamin E against atherosclerosis is exerted.

Keywords

Protein Kinase Smooth Muscle Cell Smooth Muscle Cell Proliferation Aortic Smooth Muscle Cell Vascular Smooth Muscle Cell Proliferation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Nesrin K. Özer
    • 1
    • 3
  • Önder Sirikci
    • 1
  • Suzan Taha
    • 1
  • N. Kaya Engin
    • 1
  • Daniel Boscoboinik
    • 2
  • Sophie Clément
    • 2
  • Achim Stocker
    • 2
  • Angelo Azzi
    • 2
  1. 1.Department of BiochemistryFaculty of Medicine, Marmara UniversityHaydarpasa, IstanbulTurkey
  2. 2.Institut für Biochemie und MolekularbiologieUniversität BernBernSwitzerland
  3. 3.Department of BiochemistryFaculty of Medicine, Marmara UniversityHaydarpasa, IstanbulTurkey

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