Inhibition of Angiotensin II-Induced Vascular Smooth Muscle Cell Hypertrophy by Different Catechins

  • Zheng, Ying (Department of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Song, Hye-Jin (Department of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Yun, Seok-Hee (Department of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Chae, Yeon-Jeong (Department of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Jia, Hao (Department of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Kim, Chan-Hyung (Department of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Ha, Tae-Sun (Department of Pediatrics, College of Medicine, Chungbuk National University) ;
  • Sachinidis, Agapios (Center of Physiology and Pathophysiology, University of Cologne) ;
  • Ahn, Hee-Yul (Department of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Davidge, Sandra T. (Department of Obstetrics and Gynecology and Physiology, Perinatal Research Center, University of Alberta)
  • Published : 2005.04.21

Abstract

A cumulative evidence indicates that consumption of tea catechin, flavan-3-ol derived from green tea leaves, lowers the risk of cardiovascular diseases. However, a precise mechanism for this cardiovascular action has not yet been fully understood. In the present study, we investigated the effects of different green tea catechins, such as epigallocatechin-3 gallate (EGCG), epigallocatechin (EGC), epicatechin-3 gallate (ECG), and epicatechin (EC), on angiotensin II (Ang II)-induced hypertrophy in primary cultured rat aortic vascular smooth muscle cell (VSMC). [$^3H$]-leucine incorporation was used to assess VSMC hypertrophy, protein kinase assay, and western blot analysis were used to assess mitogen-activated protein kinase (MAPK) activity, and RT-PCR was used to assess c-jun or c-fos transcription. Ang II increased [$^3H$]-leucine incorporation into VSMC. However, EGCG and ECG, but not EGC or EC, inhibited [$^3H$]-leucine incorporation increased by Ang II. Ang II increased phosphorylation of c-Jun, extracellular-signal regulated kinase (ERK) 1/2 and p38 MAPK in VSMC, however, EGCG and ECG , but not EGC or EC, attenuated c-Jun phosphorylation increased by Ang II. ERK 1/2 and p38 MAPK phosphorylation induced by Ang II were not affected by any catechins. Ang II increased c-jun and c-fos mRNA expression in VSMC, however, EGCG inhibited c-jun but not c-fos mRNA expression induced by Ang II. ECG, EGC and EC did not affect c-jun or c-fos mRNA expression induced by Ang II. Our findings indicate that the galloyl group in the position 3 of the catechin structure of EGCG or ECG is essential for inhibiting VSMC hypertrophy induced by Ang II via the specific inhibition of JNK signaling pathway, which may explain the beneficial effects of green tea catechin on the pathogenesis of cardiovascular diseases observed in several epidemiological studies.

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