Document Detail

Red wine polyphenols inhibit proliferation of vascular smooth muscle cells and downregulate expression of cyclin A gene.
MedLine Citation:
PMID:  10683356     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Red wine polyphenols have been shown to contribute to the "French paradox" phenomenon, which consists of lower morbidity and mortality from coronary heart disease in the French population. Although vascular smooth muscle cell (VSMC) proliferation plays an important role in the progression of atherosclerotic lesions, the effects of red wine polyphenols on VSMC proliferation have not been elucidated. METHODS AND RESULTS: We extracted the total polyphenolic fraction from red wine (RW-PF) by column chromatography. Treatment with RW-PF showed a potent inhibitory effect on the proliferation and DNA synthesis of cultured rat aortic smooth muscle cells (RASMCs). In contrast, the inhibitory effect of RW-PF on the proliferation of bovine carotid endothelial cells was observed only at much higher concentrations. To elucidate the molecular mechanisms of this antiproliferative effect of RW-PF on RASMCs, we investigated the effects of RW-PF on cell cycle regulation. RW-PF downregulated the expression of cyclin A mRNA and cyclin A promoter activity. In addition, RW-PF decreased the binding of nuclear proteins to the activating transcription factor (ATF) site in the cyclin A promoter and downregulated the mRNA levels of transcription factors, cAMP-responsive element-binding protein (CREB), and ATF-1. CONCLUSIONS: These results suggest that the downregulation of cyclin A gene expression may contribute to the antiproliferative effect of red wine polyphenols on RASMCs through the inhibition of transcription factor expression.
K Iijima; M Yoshizumi; M Hashimoto; S Kim; M Eto; J Ako; Y Q Liang; N Sudoh; K Hosoda; K Nakahara; K Toba; Y Ouchi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  101     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-08     Completed Date:  2000-03-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  805-11     Citation Subset:  AIM; IM    
Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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MeSH Terms
Aorta / cytology
Carotid Arteries / cytology
Cell Division / drug effects
Cells, Cultured
Cyclin A / genetics*
DNA / biosynthesis
Endothelium, Vascular / cytology,  drug effects,  metabolism
Gene Expression / drug effects*
Muscle, Smooth, Vascular / cytology*,  drug effects,  metabolism
Phenols / pharmacology*
Polymers / pharmacology*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Cyclin A; 0/Flavonoids; 0/Phenols; 0/Polymers; 0/polyphenols; 9007-49-2/DNA

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