title: Epigallocatechin-3-O-gallate inhibits the angiotensin II-induced adhesion molecule expression in human umbilical vein endothelial cell via inhibition of MAPK pathways.
abstract: 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Chungbuk University, Cheongju, South Korea.
authors.forename: Yeon Jeong
authors.initials: YJ
authors.lastname: Chae
authors.forename: Chan Hyung
authors.initials: CH
authors.lastname: Kim
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Ha
authors.forename: Jurgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Hee Yul
authors.initials: HY
authors.lastname: Ahn
authors.forename: Agapios
authors.initials: A
authors.lastname: Sachinidis
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D002392:Catechin; C045651:epigallocatechin gallate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one