Green tea catechins inhibit neointimal hyperplasia in a rat carotid arterial injury model by TIMP-2 overexpression

Abstract

Objective: Although it has been demonstrated that the antioxidant properties of tea catechins reduce athrosclerotic lesions in various animal models of hyperlipidemia, it is not yet clear whether these catechins prevent hyperlipidemia-independent arterial remodeling induced by balloon angioplasty. We evaluated the influence of the administration of the tea extract on vascular remodeling in a rat carotid artery balloon-injury model. Methods and results: Male Wistar rats were supplied drinking water with or without green tea extract (1 mg/ml) supplement. Administration of the tea extract reduced the area of the intima (30%) and the ratio of the intimal area to the medial area (36.2%) in injured arteries compared with those of control rats at 14 days after the injury. Real-time RT-PCR, Western blot, and gelatin zymography revealed a significant increase in tissue inhibitor of matrix metalloproteinase (MMP)-2 (TIMP-2) expression as well as a significant reduction of gelatinolytic net activity and activated MMP-2 levels in the injured arteries as a result of the administration of the tea extract compared with those of control group. Similarly, epigallocatechin-3-gallate, a major constituent of green tea catechins, significantly upregulated TIMP-2 expression in cultured smooth muscle cells. Immunohistochemical analysis showed that the increase of TIMP-2 protein occurred preferentially in the developing neointima. Conclusion: These results indicate that catechins inhibit intimal hyperplasia in a rat balloon-injury model through the upregulation of TIMP-2 expression to modulate MMP activity.

Smooth muscle, Matrix metalloproteinase, Restenosis