Chae Yeon Jeong, Kim Chan Hyung, Ha Tae Sun, Hescheler Jurgen, Ahn Hee Yul, Sachinidis Agapios
Department of Pharmacology, College of Medicine, Chungbuk University, Cheongju, South Korea.
Cell Physiol Biochem. 2007;20(6):859-66. doi: 10.1159/000110446.
Epigallocatechin-3-O-gallate (EGCG) is the main catechin, which is derived from Camellia sinensis plant. Vascular cell adhesion molecules (VCAMs) and intercellular adhesion molecules (ICAMs) mediate the binding of inflammatory cells onto the vascular wall-promoting the early phase of atherosclerosis. In the present study, we investigated the mechanism(s) by which EGCG inhibits angiotensin II (Ang II)-induced elevation of the membrane associated VCAM-1 and ICAM-1 in human umbilical vein endothelial cells (HUVEC). Ang II induced a 40% increase of VCAM-1 and ICAM-1 in the plasma membrane. EGCG (10 to 50 microM) inhibited the effect of Ang II in a concentration-dependent manner. In parallel, the Ang II-induced elevation of the mRNA expressions of VCAM-1 and ICAM-1 in HUVEC were completely inhibited by 50 microM EGCG. Since mitogen-activated protein kinase (MAPK) families are involved in vascular inflammation in response to stressful stimuli, we investigated the effects of EGCG on the MAPK signal transduction pathway stimulated by Ang II. EGCG (30 to 50 microM) completely inhibited the Ang II-induced phosphorylation of ERK (extracellular signal-regulated kinase) 1/2 and p38 MAPK. PD98059, an inhibitor of ERK1/2 inhibited the Ang II-induced increase of VCAM-1 but not of ICAM-1 in the plasma membranes. In contrast, SB203580, an inhibitor of p38 MAPK inhibited both the Ang II-induced enrichment of ICAM-1 and VCAM-1. From these results, it may be concluded that EGCG inhibits the Ang II-induced elevation of VCAM-1 and ICAM-1 in the HUVEC plasma membranes via inhibition of the p38 MAPK and the ERK1/2 signalling pathways resulting in an inhibition of the VCAM-1 and ICAM-1 transcription.
表没食子儿茶素-3-没食子酸酯（EGCG）是主要的儿茶素，它源自茶树植物。血管细胞黏附分子（VCAMs）和细胞间黏附分子（ICAMs）介导炎症细胞与血管壁的结合，促进动脉粥样硬化的早期阶段。在本研究中，我们探究了EGCG抑制血管紧张素II（Ang II）诱导的人脐静脉内皮细胞（HUVEC）中膜相关VCAM-1和ICAM-1升高的机制。Ang II诱导质膜中VCAM-1和ICAM-1增加40%。EGCG（10至50微摩尔）以浓度依赖的方式抑制Ang II的作用。同时，50微摩尔EGCG完全抑制了Ang II诱导的HUVEC中VCAM-1和ICAM-1 mRNA表达的升高。由于丝裂原活化蛋白激酶（MAPK）家族参与对应激刺激的血管炎症反应，我们研究了EGCG对Ang II刺激的MAPK信号转导通路的影响。EGCG（30至50微摩尔）完全抑制了Ang II诱导的细胞外信号调节激酶（ERK）1/2和p38 MAPK的磷酸化。ERK1/2抑制剂PD98059抑制了Ang II诱导的质膜中VCAM-1的增加，但未抑制ICAM-1的增加。相反，p38 MAPK抑制剂SB203580抑制了Ang II诱导的ICAM-1和VCAM-1的富集。从这些结果可以得出结论，EGCG通过抑制p38 MAPK和ERK1/2信号通路，抑制HUVEC质膜中Ang II诱导的VCAM-1和ICAM-1升高，从而抑制VCAM-1和ICAM-1的转录。
