Details

Autor(en) / Beteiligte

• SAWADA, N
• ITOH, H
• SAKAGUCHI, S
• ARAI, H
• OHNO, N
• KOMEDA, M
• NAKAO, K
• UEYAMA, K
• YAMASHITA, J
• DOI, K
• CHUN, T.-H
• INOUE, M
• MASATSUGU, K
• SAITO, T
• FUKUNAGA, Y

Titel

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

Ist Teil von

• Circulation (New York, N.Y.), 2000-05, Vol.101 (17), p.2030-2033

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2000

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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.