Catechins prevent vascular smooth muscle cell invasion by inhibiting MT1-MMP activity and MMP-2 expression
Catechins prevent vascular smooth muscle cell invasion by inhibiting MT1-MMP activity and MMP-2 expression
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DOI：
10.1016/j.cardiores.2005.03.017
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发表时间：
2005-08-01
影响因子：
10.8
通讯作者：
Schini-Kerth, VB
中科院分区：
文献类型：
--
作者：
El Bedoui, J;Oak, MH;Schini-Kerth, VB
目的：经常饮用绿色茶可降低冠心病和癌症的死亡风险。本研究探讨是否绿色茶提取物（GTE）抑制激活基质金属蛋白酶-2（MMP-2），一个主要的胶原酶参与动脉粥样硬化斑块的血管重塑，在血管平滑肌细胞（VSMCs）。方法和结果：MMP-2的表达进行了评估，通过北方和Western印迹分析在人主动脉VSMCs。MMP-2活性通过酶谱法进行评价，膜型1-MMP（MT 1-MMP，MMP-14）活性通过酶法进行评价，并且细胞侵袭通过改良的Boyden小室法进行评价。GTE和绿色茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）和（-）-表儿茶素-3-没食子酸酯（ECG）可消除凝血酶诱导的分泌型MMP-2的激活。GTE可降低MMP-2 mRNA和蛋白的表达。GTE，EGCG和ECG直接抑制细胞相关的MT 1-MMP活性，MMP-2的生理激活剂，以可逆的方式。结论：GTE抑制凝血酶诱导的VSMCs侵袭可能是通过直接抑制MT 1-MMP抑制MMP-2的表达和激活。绿色茶防止细胞侵入和基质降解的能力可能有助于其对动脉粥样硬化和癌症的保护作用。(c)2005年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
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 metalloprotemase-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-type 1-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. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.