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Resveratrol Inhibits TNF-alpha?Induced Proliferation and Matrix Metalloproteinase Expression in Human Vascular Smooth Muscle Cells

Reveratrol is polyphenol found in red grape skin. It is known that red wine reduces the risk of heart diseases and that the main phytochemical in red wine responsible for this action is resveratrol. Many studies have shown that resveratrol has anti-inflammatory, antimutagenic and antiplatelet effects. Resveratrol reduces cell proliferation and tumour progression. Resveratrol might play a role in preventing the development of atherosclerotic disease through its antiatherogenic effect on vascular smooth muscle cells. Atherosclerosis is caused by the proliferation of vascular smooth cells. Vascular lesions are associated with accumulation of inflammatory cells and the release of cytokines. Cytokines, such as tumour necrosis factor-alpha, are proteins which regulate immunity and inflammation and act by binding to membrane receptors which release messengers. Tyrosine kinase is a messenger that alters the behaviour or gene expression of cells, leading to changed cell proliferation. The purpose of this study was to investigate the effect of resveratrol on cell proliferation, cell-cycle regulation and matrix metalloproteinase-9 expression in tumour necrosis factor-alpha induced human vascular smooth cells.

Resveratrol significantly inhibited DNA synthesis in cultured vascular smooth cells in the presence of the cytokine tumor necrosis factor-alpha. Resveratrol stopped the cell cycle in the G1 phase and reduced levels of extracellular signal regulated kinase. The arrest of cells in the G1 phase was also illustrated in other studies using different cell lines. Resveratrol downregulated the exression of cyclins and cyclin dependent kinases and upregulated the expression of the cyclin dependent kinase inhibitor P21/WAF1. Resveratrol inhibited the expression of matrix metalloproteinase-9, induced by the cytokine tumor necrosis factor-alpha, by suppressing NF-kappa-B and AP-1 binding activities. Matrix metalloproteinase-9 is an important factor in the development of atherosclerosis and repair of blood vessels.

The study concluded that resveratrol inhibits cell proliferation , G1 and S phase cell cycle progress and matrix metalloproteinase-9 expression through the transcription factors in vascular smooth cells, induced by tumor necrosis factor-alpha.


Source: Beobyi Lee and Sung-Kwon Moon. Resveratrol Inhibits TNF-alpha?Induced Proliferation and Matrix Metalloproteinase Expression in Human Vascular Smooth Muscle Cells. Journal of Nutrition, 135:2767-2773, December 2005


 
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