Rho-kinase inhibitor suppressed restenosis in porcine coronary balloon angioplasty.
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.
Iso
Yoshitaka
Y
Third Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Suzuki
Hiroshi
H
Sato
Takatoshi
T
Shoji
Makoto
M
Shimizu
Nobuyuki
N
Shibata
Masayuki
M
Koba
Shinji
S
Geshi
Eiichi
E
Katagiri
Takashi
T
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
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