Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits

Tadashi Furuyama, Kimihiro Komori, Hiroaki Shimokawa, Yasuharu Matsumoto, Toyokazu Uwatoku, Katsuya Hirano, Yoshihiko Maehara

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Rho kinase plays an important role in vascular smooth muscle cell (VSMC) contraction and other cellular functions, such as proliferation, migration, and apoptosis. Recent studies have demonstrated that long-term inhibition of Rho kinase suppresses coronary artery spasm and vascular lesion formation after arterial injury. In the cardiovascular surgery field, intimal thickening in vein grafts is the major cause of late graft failure, for which no effective treatment has yet been developed. In this study, we examined whether long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. Methods: Male rabbits were randomly divided into two groups and received normal chow (control group) or a special chow containing 0.09% fasudil (fasudil group). After oral administration, fasudil is metabolized to a specific Rho kinase inhibitor, hydroxyfasudil. Each group underwent reversed autologous vein graft surgery with the internal jugular vein into the left common carotid artery. At 1, 2, and 4 weeks after the operation, we examined the extent of intimal thickening of the graft and VSMC proliferation and apoptosis. Results: The intimal thickening was significantly suppressed in the fasudil group compared with the control group at 2 and 4 weeks after the operation. In the fasudil group, VSMC proliferation was suppressed at 1 and 2 weeks after the operation, whereas VSMC apoptosis was enhanced at 2 weeks after the procedure. Conclusions: These results indicate that Rho kinase is substantially involved in the pathogenesis of intimal thickening of vein grafts and that it is an important therapeutic target for the prevention of graft failure.

Original languageEnglish
Pages (from-to)1249-1256
Number of pages8
JournalJournal of Vascular Surgery
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 1 2006

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Tunica Intima
rho-Associated Kinases
Veins
Rabbits
Transplants
Vascular Smooth Muscle
Smooth Muscle Myocytes
Apoptosis
Cell Proliferation
Control Groups
Common Carotid Artery
Jugular Veins
Spasm
Muscle Contraction
Blood Vessels
Oral Administration
Coronary Vessels
fasudil
Wounds and Injuries
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

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Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. / Furuyama, Tadashi; Komori, Kimihiro; Shimokawa, Hiroaki; Matsumoto, Yasuharu; Uwatoku, Toyokazu; Hirano, Katsuya; Maehara, Yoshihiko.

In: Journal of Vascular Surgery, Vol. 43, No. 6, 01.06.2006, p. 1249-1256.

Research output: Contribution to journalArticle

Furuyama, Tadashi ; Komori, Kimihiro ; Shimokawa, Hiroaki ; Matsumoto, Yasuharu ; Uwatoku, Toyokazu ; Hirano, Katsuya ; Maehara, Yoshihiko. / Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. In: Journal of Vascular Surgery. 2006 ; Vol. 43, No. 6. pp. 1249-1256.
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