Inhibition of Rho-associated kinase results in suppression of neointimal formation of balloon-injured arteries

Naoki Sawada, Hiroshi Itoh, Koji Ueyama, Jun Yamashita, Kentaro Doi, Tae Hwa Chun, Mayumi Inoue, Ken Masatsugu, Takatoshi Saito, Yasutomo Fukunaga, Satsuki Sakaguchi, Hiroshi Arai, Nobuhisa Ohno, Masashi Komeda, Kazuwa Nakao

研究成果: Article査読

184 被引用数 (Scopus)

抄録

Background - Rho-associated kinase (ROCK), an effector of small GTPase Rho, regulates vascular tone via a calcium sensitization mechanism and plays a key role in the pathogenesis of hypertension. However, its role in vascular growth remains unclear. Methods and Results - Y-27632, a specific ROCK inhibitor, and the overexpression of dominant-negative ROCK suppressed the mitogen-induced DNA synthesis of cultured vascular smooth muscle cells (VSMCs), which indicates the essential role of ROCK in the control of VSMC proliferation in vitro. Y-27632 also suppressed the chemotaxis of VSMCs. Male Wistar rats were systemically given Y-27632 (35 to 70 mg · kg-1 · day- 1) through an intraperitoneal infusion. The neointimal formation of balloon- injured carotid arteries was significantly suppressed in Y-27632-treated rats (intima/media ratio, 0.22±0.02) compared with vehicle-treated rats (intima/media ratio, 0.92±0.21) or hydralazine-treated rats with a similar blood pressure decrease (intima/media ratio, 1.03±0.15). The phosphorylation of myosin phosphatase and myosin light chain was elevated in injured arteries in a Y-27632-sensitive manner, indicating the augmentation of ROCK activity in neointimal formation. The downregulation of the cyclin-dependent kinase inhibitor p27(kip1) in injured vessels was reversed by Y-27632 treatment, reflecting the antiproliferative effect of ROCK inhibition in vivo. Conclusions - We conclude that ROCK plays a key role in the process of neointimal formation after balloon injury. Thus, the inhibition of ROCK may be a potential therapeutic strategy for treating vascular proliferative disorders and hypertension.

本文言語English
ページ(範囲)2030-2033
ページ数4
ジャーナルCirculation
101
17
DOI
出版ステータスPublished - 2000 5月 2
外部発表はい

ASJC Scopus subject areas

  • 循環器および心血管医学
  • 生理学(医学)

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