| Co-Investigator(Kenkyū-buntansha) |
KOMORI Kimihiro Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (40225587)
YAMAMOTO Kiyohito University Hospital, Assistant Professor, 医学部附属病院, 講師 (10298359)
KAIBUCHI Kouzou Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (00169377)
AMANO Mutsuki Nagoya University, Graduate School of Medicine, Assistant Professor, 大学院医学系研究科, 講師 (90304170)
KATONO Yuki University Hospital, Hospital, Research Associate, 医学部附属病院, 病院助手 (30378088)
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| Research Abstract |
The efficacy of statin, a hydrophilic statin, pravastatin, and a lipohylic statin, pitavastatin, were evaluated on intimal hyperplasia, Rho-kinesis, and midkine expression of experimental normocholesterolemic rabbit autologous vein graft. Rabbit were fed regular rabbit chow, and pravastatin (10mg/kg/day), and pitavastatin (1mg/kg/day) was administered, respectively. A week after starting the treatment, juglar vein was implanted into the carotid artery. At 2 and 4 weeks after the operation, vein graft were harvested, and intimal hyperplasia of the vein grafts were assessed. Cell proliferation in neointima was detected by PCNA and Ki-67 stain 2 weeks after implantation. In addition, the effect of pitavastatin on midkine expression, a heparin-binding growth factor, in vein grafts was analyzed by Western blotting. And also the effect of pravastatin on human umbilical vein endothelial cells and vascular smooth muscle cells were examined by Westernblotting. We demonstrated that oral administ
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ration of both pravastatin and pitavastatin to normocholesterolemic rabbits inhibited intimal hyperplasia of carotid interposition-reversed juglar vein grafts after implantation and suppressed cell proliferation and apoptosis in theneointima. In addition, we found that pravasatatin inhibited Rho-kinase activity and accelerated endothelial nitric oxide synthase expression in human unbilical vein endothelial cells but did not inhibit Rho-kinase activity in vascular smooth muscle cells. As to pitavasatin, we found that pitavastatin inhibited midkine expression significantly in the vein grafts after implantation
These novel findings clearly demonstrated that both hydrophilic and lipohylic statin can suppress intimal hyperplasia of the vein graft in vivo, and a hydrophilic statin show endothelial cell-tropic inhibition of Rho-kinase in vitro, while a lipophilic statin show midkine inhibition. These results strongly support the clinical use of statins to prevent intimal hyperplasia of the vein graft after bypass grafting. Less
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