title: Inhibitory effect of epigallocatechin 3-O-gallate on vascular smooth muscle cell hypertrophy induced by angiotensin II.
abstract: Recent evidence indicates that epigallocatechin 3-O-gallate (EGCG), the major catechin derived from green tea leaves, lowers the risk of cardiovascular diseases such as atherosclerosis and hypertension. However, a precise mechanism for this biologic function has not yet been clearly delineated. Angiotensin II (Ang II) stimulates vascular smooth muscle cell (VSMC) hypertrophy, which is a critical event in the development of atherosclerosis, hypertension, and angioplasty-induced restenosis. In the present study, we show that EGCG inhibits Ang II-stimulated VSMC hypertrophy, as determined by [3H]leucine incorporation into VSMC. Since mitogen-activated protein kinase (MAPK) families are involved in cell growth, we determined whether EGCG affects them. EGCG pretreatment did not exert any significant changes in Ang II-stimulated activation of extracellular signal-regulated kinase (ERK) and p38 MAPK. EGCG only inhibited Ang II-stimulated activation of c-Jun N-terminal kinase (JNK). Moreover, EGCG suppressed Ang II-induced c-jun mRNA expression. In contrast, EGC, a structural analogue of EGCG, did not inhibit the JNK activity or c-jun mRNA expression. In addition, a specific JNK inhibitor, SP600125, dose-dependently suppressed Ang II-stimulated VSMC hypertrophy. These results suggest that the effect of EGCG on Ang II-induced VSMC hypertrophy is due to specific inhibition of the JNK signaling pathway at both transcriptional and posttranslational levels, which may underlie its beneficial effect on the cardiovascular diseases.
authors.affiliation: Department of Pharmacology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Song
authors.forename: Chan Hyung
authors.initials: CH
authors.lastname: Kim
authors.forename: Hun Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Eung-Gook
authors.initials: EG
authors.lastname: Kim
authors.forename: Agapios
authors.initials: A
authors.lastname: Sachinidis
authors.forename: Hee Yul
authors.initials: HY
authors.lastname: Ahn
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018696:Neuroprotective Agents; D000804:Angiotensin II; D002392:Catechin; C045651:epigallocatechin gallate; D020929:Mitogen-Activated Protein Kinase Kinases