Exp Mol Med.  2006 Oct;38(5):525-534.

Catechins inhibit angiotensin II-induced vascular smooth muscle cell proliferation via mitogen-activated protein kinase pathway

• Won SM
• Park YH
• Kim HJ
• Park KM
• Lee WJ

Abstract

Catechins, components of green tea, reduce the incidence of cardiovascular diseases such as atherosclerosis. Angiotensin II (Ang II) is highly implicated in the proliferation of vascular smooth muscle cells (VSMC), resulting in atherosclerosis. The acting mechanisms of the catechins remain to be defined in the proliferation of VSMC induced by Ang II. Here we report that catechin, epicatechin (EC), epicatechingallate (ECG) or epigallocatechingallate (EGCG) significantly inhibits the Ang II-induced [3H]thymidine incorporation into the primary cultured rat aortic VSMC. Ang II increases the phosphorylation of the extracellular signal-regulated protein kinase 1/2 (ERK 1/2), c-jun-N-terminal kinase 1/2 (JNK 1/2), or p38 mitogen-activated protein kinases (MAPKs) and mRNA expression of c-jun and c-fos. The EGCG pretreatment inhibits the Ang II-induced phosphorylation of ERK 1/2, JNK 1/2, or p38 MAPK, and the expression of c-jun or c-fos mRNA. U0126, a MEK inhibitor, SP600125, a JNK inhibitor, or SB203580, a p38 inhibitor, attenuates the Ang II-induced [3H]thymidine incorporation into the VSMC. In conclusion, catechins inhibit the Ang II-stimulated VSMC proliferation via the inhibition of the Ang II-stimulated activation of MAPK and activator protein-1 signaling pathways. The antiproliferative effect of catechins may be associated with the reduced risk of cardiovascular diseases by the intake of green tea. Catechins may be useful in the development of prevention and therapeutics of vascular diseases.

Keyword

angiotensin II; catechin; mitogen-activated protein kinase; muscle, smooth, vascular; proto-oncogene proteins c-fos; proto-oncogene proteins c-jun

MeSH Terms

Signal Transduction/drug effects
Rats, Sprague-Dawley
Rats
RNA, Messenger/metabolism
Proto-Oncogene Proteins c-jun/metabolism
Proto-Oncogene Proteins c-fos/metabolism
Phosphorylation
Nucleic Acid Synthesis Inhibitors/pharmacology
Muscle, Smooth, Vascular/cytology/*drug effects
Mitogen-Activated Protein Kinases/*metabolism/physiology
Female
DNA/biosynthesis
Cells, Cultured
Cell Proliferation/*drug effects
Cell Culture Techniques
Catechin/analogs & derivatives/*pharmacology/physiology
Animals
Angiotensin II/*pharmacology