Mechanisms of the inhibitory effect of epigallocatechin-3-gallate on cultured human vascular smooth muscle cell invasion

Xian Wu Cheng, Masafumi Kuzuya, Kae Nakamura, Zexuan Liu, Qun Di, Jun Hasegawa, Mitsunaga Iwata, Toyoaki Murohara, Mitsuhiro Yokota, Akihisa Iguchi

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Abstract

Objective - Although we recently showed that the administration of catechins reduced the neointimal formation in a rat balloon-injury model, the precise molecular mechanisms are largely unknown. In the present study, we tried to determine these mechanisms using an in vitro SMC invasion system. Methods and Results - Boyden chamber assay was used to examine the effect of catechins on the invasive behavior of SMCs. The invasive activity of SMCs through collagen gel was restrained by EGCG in a concentration-dependent manner. The data from gelatin and collagen zymography and Western blot revealed that EGCG blocks the activation of pro-matrix metalloproteinase (MMP)-2 during an invasion assay and in the conditioned medium of cultured SMCs as well as the activities of MMP-2 and membrane type 1-MMP (MT1-MMP) even at 0.1 to 0.3 μmol/L of EGCG. EGCG was found to restrain MT1-MMPcat-dependent pro-MMP-2 activation. EGCG upregulated the expression of tissue inhibitor of MMP-2 (TIMP-2) protein. Reverse zymography showed that the increased TIMP-2 to expression was validated by an increased activity. The data from decreased TIMP-2 activity using its siRNA suggested that upregulation of TIMP-2 expression may be one of the major mechanisms for inhibition of SMC invasion by EGCG. Conclusions - These results indicate that EGCG targets multiple MMP-mediated SMC cellular events and provides a new major mechanism for the SMC invasion through upregulation of TIMP-2 expression to modulate MMP activity.

Original languageEnglish
Pages (from-to)1864-1870
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number9
DOIs
Publication statusPublished - 01-09-2005

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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