title: Rho-kinase inhibitor suppressed restenosis in porcine coronary balloon angioplasty.
abstract: 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.
  
  
  CONCLUSIONS
  Local delivery of Y-27632 suppressed constrictive remodeling as well as neointimal formation after coronary balloon angioplasty in pigs.
authors.affiliation: Third Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iso
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sato
authors.forename: Makoto
authors.initials: M
authors.lastname: Shoji
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibata
authors.forename: Shinji
authors.initials: S
authors.lastname: Koba
authors.forename: Eiichi
authors.initials: E
authors.lastname: Geshi
authors.forename: Takashi
authors.initials: T
authors.lastname: Katagiri
mesh_terms: D000577:Amides / Q000494:pharmacology*; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects*; D014463:Ultrasonography; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases