Local delivery of green tea catechins inhibits neointimal formation in the rat carotid artery injury model

Abstract

It has been shown that green tea catechins (GTC) suppress proliferation of vascular smooth muscle cells (VSMCs) and that epigallocatechin-3-gallate (EGCG), which is a major constituent of GTC, selectively inhibits the platelet-derived growth factor-BB (PDGF-BB)-induced intracellular signaling transduction pathway. Vascular smooth muscle cell proliferation is one of major mechanisms of restenosis following percutaneous coronary intervention. This study tested whether GTC can inhibit VSMC proliferation and prevent neointimal formation in a rat carotid artery injury model. Vascular smooth muscle cell proliferation inhibition was analyzed with [3H]thymidine incorporation. Green tea catechins were applied to the endothelium-denuded carotid arteries of rats for 20 min. Angiography and morphometric analysis was performed after 2 weeks. Green tea catechins decreased [3H]thymidine incorporation stimulated with PDGF-BB dose dependently. In the absence of PDGF-BB, the decrement of [3H]thymidine incorporation was evident above a concentration of 10 micro g/ml of GTC. Carotid arteriographic evaluation showed that the minimum luminal diameter in the GTC-treated group (n=12) was 5.9 +/- 1.6 arbitrary units (a.u.) and was significantly larger than in the control group (4.3 +/- 1.4 a.u., n=10) ( P <0.05). The GTC-treated group also showed a significant reduction in neointimal formation compared with the control group (0.29 +/- 0.11 vs 0.42 +/- 0.10 mm2, P < 0.05). To identify the active ingredients, we performed a similar experiment using EGCG. The effects of EGCG were similar to those of GTC. Green tea catechins effectively inhibited VSMC proliferation. Neointimal formation was prevented in the rat carotid artery injury model by local delivery of GTC. As EGCG showed similar effects, it may be one of the major constituents of GTC having these effects.

Tea polyphenols inhibit rat vascular smooth muscle cell adhesion and migration on collagen and laminin via interference with cell–ECM interaction

“…For example, EGCG has been shown to bind PDGF receptor and inhibits its signaling in human SMC [11]. Catechins can inhibit the cultured smooth muscle cell invasion through the basement barrier [12] and inhibit neointimal hyperplasia by inducing TIMP-2 overexpression in the rat carotid artery injury model [13]. One of the action mechanisms of EGCG has been described to inhibit the activation of pro-matrix metalloproteinase (MMP)-2 and the activities of membrane type 1-MMP (MT1-MMP) [14].…”

Inhibition of aortic intimal hyperplasia and cell cycle protein and extracellular matrix protein expressions by BuYang HuanWu Decoction

“…This characteristic of TCM and TCM formula is particularly relevant to the inhibition of VSMC proliferation that is often associated with multiple mechanisms. Previous studies indicated that numerous medicinal plants and their components possess inhibitive activity on VSMC proliferation and are effective for attenuation of the restenosis after PTCA by aiming to multiple targets and through multiple mechanisms (Pan et al, 2003;Kim et al, 2004;Wang et al, 2007). But the disadvantages in TCM and TCM formula are also obvious including the crude and inconsistent preparation, unstable quality and the lack of defined mechanism of effects.…”

The effects of BuYang HuanWu Decoction and its effective components on proliferation-related factors and ERK1/2 signal transduction pathway in cultured vascular smooth muscle cells

“…TCM formulations have multiple functional components that interact with multiple biological targets, resulting in a holistic effect that can positively influence the development of complex chronic diseases. Many studies (Pan et al, 2003;Kim et al, 2004) showed that a variety of medicinal plants and their ingredients had the ability to inhibit VSMC proliferation and diminish post PCI restenosis. But further studies using standardized TCM extracts are still necessary to investigate pharmacological efficacy and biomechanic pathways.…”