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Effects of statin on vascular diseases-inhibitory mechanism on intimal hyperplasia

他汀类药物对血管疾病的影响——内膜增生的抑制机制

基本信息

批准号：
17591326
负责人：
KOBAYASHI Masayoshi
金额：
$ 2.24万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591326/
关键词：
statin inhibition of intimal hyperplasia autologous vein graft Rho-kinesis eNOS midkine Rho-kinase

项目摘要

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 … More 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 implantationThese 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

他汀类药物、亲水他汀类药物普伐他汀类药物和降脂他汀类药物匹伐他汀类药物对实验性正常胆固醇血症兔自体静脉移植物内膜增生、Rho-kinesis和midkine表达的影响进行了评估。兔饲喂普通兔粮，分别饲喂普伐他汀（10mg/kg/d）和匹伐他汀（1mg/kg/d）。治疗开始一周后，将颈静脉植入颈动脉。术后2周、4周取静脉移植物，观察血管内膜增生情况。植入2周后用PCNA和Ki-67染色检测内膜细胞增殖情况。Western blotting分析匹伐他汀对移植静脉中肝素结合生长因子midkine表达的影响。并采用Westernblotting检测普伐他汀对人脐静脉内皮细胞和血管平滑肌细胞的影响。结果表明，正常胆固醇血症家兔口服较多普伐他汀和匹伐他汀可抑制颈动脉介入逆转颈静脉移植物移植后的内膜增生，抑制内膜细胞增殖和凋亡。此外，我们发现普伐他汀抑制人脐静脉内皮细胞的rho激酶活性，加速内皮型一氧化氮合酶的表达，但不抑制血管平滑肌细胞的rho激酶活性。对于匹伐他汀，我们发现匹伐他汀在静脉移植后显著抑制midkine的表达。这些新发现清楚地表明，亲水和脂质他汀在体内都能抑制静脉移植的内膜增生，并且在体外，亲水他汀对rhok的内皮细胞有抑制作用，而亲脂性他汀对midkine有抑制作用。这些结果有力地支持了临床应用他汀类药物预防旁路移植术后血管内膜增生。少

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

血管疾患を知る

了解血管疾病

DOI：
发表时间：
2005
期刊：
影响因子：
0
作者：
辰巳哲也;松原弘明
通讯作者：
松原弘明

Hydrophilic statin suppresses vein graft intimal hyperplasia via endothelial cell-tropic Rho-kinase inhibition

DOI：
10.1016/j.jvs.2005.05.041
发表时间：
2005-10-01
期刊：
JOURNAL OF VASCULAR SURGERY
影响因子：
4.3
作者：
Yamanouchi, D;Banno, H;Komori, K
通讯作者：
Komori, K

Ex vivo electroporation as a potent new strategy for nonviral gene transfer into autologous vein grafts

离体电穿孔作为非病毒基因转移至自体静脉移植物的有效新策略

DOI：
发表时间：
2005
期刊：
Am J Physiol 289
影响因子：
0
作者：
松浦成昭;横山雄起;他;門田守人;Kajiguchi M;Fujishiro K;Takeda H;Kobayashi K;Furuyama T;Bannno H;Hayashi K;Yamaoka T
通讯作者：
Yamaoka T

Clinical protocol for angiogenesis by intramyocardial injection of autologous bone marrow mononuclear cells in patients with severe coronary artery disease: TACT-NAGOYA-HEART.

严重冠状动脉疾病患者心肌内注射自体骨髓单核细胞进行血管生成的临床方案：TACT-NAGOYA-HEART。