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IR@PKUHSC  > 北京大学第二临床医学院  > 血管外科  > 期刊论文
学科主题: 临床医学
题名:
Fasudil, a Rho-kinase inhibitor, prevents intima-media thickening in a partially ligated carotid artery mouse model: Effects of fasudil in flow-induced vascular remodeling
作者: Zhang, Xiangyu1; Zhang, Tao1; Gao, Fu1; Li, Qingle1; Shen, Chenyang1; Li, Yankui2; Li, Wei1; Zhang, Xiaoming1
关键词: flow-induced vascular remodeling ; Rho-associated kinase pathway ; fasudil
刊名: MOLECULAR MEDICINE REPORTS
发表日期: 2015-11-01
DOI: 10.3892/mmr.2015.4409
卷: 12, 期:5, 页:7317-7325
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Medicine, Research & Experimental
研究领域[WOS]: Oncology ; Research & Experimental Medicine
关键词[WOS]: CARDIOVASCULAR RISK-FACTORS ; MYOSIN LIGHT-CHAIN ; E-DEFICIENT MICE ; PROTEIN-KINASE ; SHEAR-STRESS ; NEOINTIMAL FORMATION ; IN-VIVO ; PHOSPHORYLATION ; ATHEROSCLEROSIS ; INVOLVEMENT
英文摘要:

Vascular remodeling in response to hemodynamic alterations is a physiological process that requires coordinated signaling between endothelial, inflammatory and vascular smooth muscle cells (VSMCs). Extensive experimental and clinical studies have indicated the critical role of the Ras homolog gene family, member A/Rho-associated kinase (ROCK) signaling pathway in the pathogenesis of cardiovascular disease, where ROCK activation has been demonstrated to promote inflammation and remodeling through inducing the expression of proinflammatory cytokines and adhesion molecules in endothelial cells and VSMCs. However, the role of ROCK in flow-induced vascular remodeling has not been fully defined. The current study aimed to investigate the effect of the ROCK signaling pathway in flow-induced vascular remodeling by comparing the responses to partial carotid artery ligation in mice treated with fasudil (a ROCK inhibitor) and untreated mice. Intima-media thickness and neointima formation were evaluated by morphology. VSMC proliferation and inflammation of the vessel wall were assessed by immunohistochemistry. In addition, the expression levels of ROCK and the downstream effectors of ROCK, myosin light chain (MLC) and phosphorylated-MLC (p-MLC), were quantified by western blot analysis. Following a reduction in blood flow, ROCK1 and p-MLC expression increased in the untreated left common carotid arteries (LCA). Fasudil-treated mice developed a significantly smaller intima-media thickness compared with the untreated mice. Quantitative immunohistochemistry of the fasudil-treated LCA indicated that there was a reduction in proliferation when compared with untreated vessels. There were fewer CD45(+) cells observed in the fasudil-treated LCA compared with the untreated LCA. In conclusion, the expression of ROCK was enhanced in flow-induced carotid artery remodeling and ROCK inhibition as a result of fasudil treatment may attenuate flow-induced carotid artery remodeling.

语种: 英语
所属项目编号: 2118000537 ; 2109000075 ; 81470574
项目资助者: Peking University People&prime ; s Hospital Research and Development Funds ; Specialized Research Fund for the Doctoral Program of Higher Education of China ; National Natural Science Foundation of China
WOS记录号: WOS:000364889100016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53879
Appears in Collections:北京大学第二临床医学院_血管外科_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Dept Vasc Surg, Beijing 100044, Peoples R China
2.Tianjin Med Univ, Affiliated Hosp 2, Dept Gen Surg, Tianjin 300000, Peoples R China

Recommended Citation:
Zhang, Xiangyu,Zhang, Tao,Gao, Fu,et al. Fasudil, a Rho-kinase inhibitor, prevents intima-media thickening in a partially ligated carotid artery mouse model: Effects of fasudil in flow-induced vascular remodeling[J]. MOLECULAR MEDICINE REPORTS,2015,12(5):7317-7325.
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