PT  - JOURNAL ARTICLE
AU  - Yoshiyuki Muranaka
AU  - Yasundo Yamasaki
AU  - Yoshihisa Nozawa
AU  - Hiroshi Terakawa
AU  - Yasutaka Tanahashi
AU  - Nobuyuki Oda
AU  - Atsushi Satoh
AU  - Tetsuji Asao
AU  - Hidekazu Miyake
AU  - Naosuke Matsuura
TI  - TAS-301, an Inhibitor of Smooth Muscle Cell Migration and Proliferation, Inhibits Intimal Thickening after Balloon Injury to Rat Carotid Arteries
DP  - 1998 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1280--1286
VI  - 285
IP  - 3
4099  - http://jpet.aspetjournals.org/content/285/3/1280.short
4100  - http://jpet.aspetjournals.org/content/285/3/1280.full
SO  - J Pharmacol Exp Ther1998 Jun 01; 285
AB  - The purpose of this study was to determine the efficacy and the possible mechanism of action of a recently synthesized drug, TAS-301 [3-bis (4-methoxyphenyl)methylene-2-indolinone], on intimal formation in comparison with those of tranilast, the clinical efficacy of which was reported earlier. Rat carotid arteries were injured using a balloon catheter. Neointimal thickening, measured 14 days after injury, was reduced by the oral administration of TAS-301 in a dose-dependent fashion (3–100 mg/kg), and the effect of TAS-301 at a dose of 100 mg/kg was significantly greater than that of tranilast (300 mg/kg). Fewer cells were found on the intima of balloon-injured arteries of TAS-301-treated rats than on arteries of tranilast-treated rats. In anin vitro assay, TAS-301 inhibited the migration of smooth muscle cells (SMCs) stimulated by platelet-derived growth factor-BB, insulin-like growth factor-1 or heparin-binding epidermal growth factor-like growth factor. In addition, TAS-301 and tranilast reduced the proliferation of medial and intimal SMCs at 4 and 8 days, respectively, after the injury. In vitro, TAS-301 inhibited basic fibroblast growth factor-induced proliferation of SMCs dose dependently. These findings indicate that TAS-301 shows a higher inhibitory potency on intimal formation than tranilast due to inhibition of both migration of medial SMCs and proliferation of medial and intimal SMCs. Our results suggest that further evaluation of TAS-301 as an inhibitor of postangioplasty intimal thickening is warranted. The American Society for Pharmacology and Experimental Therapeutics