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1 Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Higashi-ku, Fukuoka 812-8582, 2 Division of Signal Transduction, Nara Institute of Science, and Technology, Nara 630-0121, Japan; and 3 Molecular Cardiology, University of California, San Diego, California 92093-0613
Restenosis after angioplasty still remains a major
problem for which neointimal formation appears to play an important
role. Recent studies in vitro suggested that Rho kinase, a target
protein of Rho, is important in various cellular functions. We thus
examined whether Rho kinase is involved in the restenotic changes after balloon injury. In vivo gene transfer was performed immediately after
balloon injury in both sides of the porcine femoral
arteries with adenoviral vector encoding either a dominant
negative form of Rho kinase (AdDNRhoK) or 
-galactosidase (AdLacZ) as
a control. One week after the transfer, immunohistochemistry confirmed
the successful gene expression in the vessel wall, whereas 2 wk after the transfer, Western blotting showed the functional upregulation of Rho kinase at the AdLacZ site and its suppression at the AdDNRhoK site. Angiography showed the development of a stenotic lesion at the
AdLacZ site where histological neointimal formation was noted, whereas
those changes were significantly suppressed at the AdDNRhoK site. These
results indicate that Rho kinase is involved in the pathogenesis of
neointimal formation after balloon injury in vivo.
restenosis; signal transduction; small guanosine 5'triphosphate-binding protein; vascular smooth muscle
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