Document Detail


Rho-kinase inhibitor suppressed restenosis in porcine coronary balloon angioplasty.
MedLine Citation:
PMID:  15922466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Constrictive remodeling is thought to be more important than neointimal formation in coronary restenosis after balloon angioplasty. The inhibition of Rho-kinase prevents neointimal proliferation, but now this inhibition that affects constrictive remodeling remains unknown. To explore this issue further, we investigated whether a specific Rho-kinase inhibitor, Y-27632, could suppress restenosis after coronary balloon angioplasty in a porcine model. METHODS: Balloon angioplasty with local administration of Y-27632 (Y group) or vehicle (C group) was performed at 2 and 3 weeks after overstretch injury in a porcine coronary artery. Quantitative coronary angiography (QCA) and quantitative coronary ultrasound (QCU) were performed to assess the coronary lesion segment. A morphometrical analysis was performed in a histological study. Proliferative cells and p27(Kip1)-positive cells were evaluated in the arterial wall using immunohistochemistry. RESULTS: QCA and QCU demonstrated that the minimal lumen diameter and minimal lumen area were greater, and % stenosis was less in the Y group than in the C group. The QCU analysis also revealed a significant inhibition in the increase of the intimal area and a prevention of constrictive remodeling by Y-27632. In the histological study, the intimal, adventitial and collagen areas were significantly smaller in the Y group than in the C group. The Y group also exhibited significantly less proliferative activity and a significantly higher percentage of cells expressing p27(Kip1) in the arterial wall. CONCLUSION: Local delivery of Y-27632 suppressed constrictive remodeling as well as neointimal formation after coronary balloon angioplasty in pigs.
Authors:
Yoshitaka Iso; Hiroshi Suzuki; Takatoshi Sato; Makoto Shoji; Nobuyuki Shimizu; Masayuki Shibata; Shinji Koba; Eiichi Geshi; Takashi Katagiri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cardiology     Volume:  106     ISSN:  0167-5273     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-02     Completed Date:  2006-03-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  103-10     Citation Subset:  IM    
Affiliation:
Third Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology*
Angioplasty, Transluminal, Percutaneous Coronary*
Animals
Coronary Restenosis / enzymology*,  prevention & control*,  ultrasonography
Enzyme Inhibitors / pharmacology*
Intracellular Signaling Peptides and Proteins
Protein-Serine-Threonine Kinases / antagonists & inhibitors*
Pyridines / pharmacology*
Swine
Tunica Intima / drug effects*
rho-Associated Kinases
Chemical
Reg. No./Substance:
0/Amides; 0/Enzyme Inhibitors; 0/Intracellular Signaling Peptides and Proteins; 0/Pyridines; 138381-45-0/Y 27632; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/rho-Associated Kinases

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