Green tea catechins inhibit the cultured smooth muscle cell invasion through the basement barrier.
Epidemiological studies suggest that green tea consumption is associated with a reduced risk of cardiovascular disease. Antioxidative properties of green tea flavonoids, catechins, have been believed to be involved in the antiatherogenic effect of green tea, since catechins inhibit low density lipoprotein oxidation. The migration of vascular smooth muscle cells (SMCs) from the tunica media to the subendothelial region is a key event in the development and progression of atherosclerosis and post-angioplasty vascular remodeling. Matrix metalloproteinases (MMPs) play a key role in these processes of SMC migration. In the present study, we investigated the effect of catechins on the gelatinolytic activity of MMP-2 that was derived from cultured bovine aortic SMCs. We also investigated the effect of catechins on the SMC invasion through the reconstituted basement membrane barrier. A major constituent of green tea catechins, (-)-epigallocatechin gallate (EGCG), inhibited the gelatinolytic activity of MMP-2 and concanavalin A (ConA)-induced pro-MMP-2 activation without the influence of membrane-type MMP expression in SMCs. EGCG also inhibited the SMC invasion through the basement membrane barrier in a concentration-dependent manner without any influence of SMC migration across the basement membrane protein thin-coated filter. The antagonistic effects of other catechins, namely (-)-epigallocatechin (EGC) and (-)-epicatechin gallate (ECG), on gelatinolytic activity of MMP-2, ConA-induced pro-MMP-2 activation, or PDGF-BB-directed SMC invasion were much less pronounced than those of EGCG. Also, (+)-catechin and (-)-epicatechin failed to show any effect. These findings may suggest that the anti-invasive and anti-metalloproteinase activities involve at least part of the anti-atherogenic action of catechin in accordance with the antioxidant properties of catechin.
Maeda
Keiko
K
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Kuzuya
Masafumi
M
Cheng
Xian Wu
XW
Asai
Toshinobu
T
Kanda
Shigeru
S
Tamaya-Mori
Norika
N
Sasaki
Takeshi
T
Shibata
Tami
T
Iguchi
Akihisa
A
D001485:Basement Membrane / Q000166:cytology; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects; D004338:Drug Combinations; D018093:Gelatinases; D006801:Humans; D007797:Laminin / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011509:Proteoglycans / Q000187:drug effects; D013662:Tea / Q000737:chemistry*
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D013662:Tea; C059485:matrigel; D002392:Catechin; D003094:Collagen; D018093:Gelatinases; D020782:Matrix Metalloproteinases