Copyright © 2005, European Society of Cardiology
Catechins prevent vascular smooth muscle cell invasion by inhibiting MT1-MMP activity and MMP-2 expression
aPharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, France
bPhysiopathologie du Système Nerveux, INSERM U.575, Université Louis Pasteur de Strasbourg, France
cResearch and Development Center, Yangji Chemicals, An-San, South Korea
* Corresponding author. UMR CNRS 7034, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, B.P. 60024, F-67401 Illkirch, France. Tel.: +33 3 90 24 41 27; fax: +33 3 90 24 43 13. Email address: schini{at}aspirine.u-strasbg.fr
Objective: Regular consumption of green tea is associated with a reduced risk of mortality due to coronary diseases and cancer. The present study examined whether a green tea extract (GTE) inhibits activation of matrix metalloproteinase-2 (MMP-2), a major collagenase involved in vascular remodeling of atherosclerotic plaques, in vascular smooth muscle cells (VSMCs).
Methods and results: The expression of MMP-2 was assessed by Northern and Western blot analyses in human aortic VSMCs. MMP-2 activity was evaluated by zymography, membrane-type1-MMP (MT1-MMP, MMP-14) activity by an enzymatic assay, and cell invasion by a modified Boyden chamber assay. The thrombin-induced activation of secreted MMP-2 was abolished by GTE and the green tea polyphenols (–)-epigallocatechin-3-gallate (EGCG) and (–)-epicatechin-3-gallate (ECG). GTE reduced the expression of MMP-2 mRNA and protein. GTE, EGCG and ECG directly inhibited cell-associated MT1-MMP activity, the physiological activator of MMP-2, in a reversible manner. Thrombin-stimulated VSMCs invasion was abolished by EGCG and ECG, and reduced by GTE.
Conclusions: GTE inhibits thrombin-induced VSMCs invasion most likely by preventing MMP-2 expression and its activation by a direct inhibition of MT1-MMP. The ability of green tea to prevent cell invasion and matrix degradation might contribute to its protective effect on atherosclerosis and cancer.
KEYWORDS Matrix metalloproteinases; Atherosclerosis; Smooth muscle
1 Both authors contributed equally to this work.
Time for primary review 19 days
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