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学科主题临床医学
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
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
2015-11-01
DOI10.3892/mmr.2015.4409
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
WOS记录号WOS:000364889100016
项目编号2118000537 ; 2109000075 ; 81470574
资助机构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
引用统计
被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53879
专题北京大学第二临床医学院_血管外科
北京大学第二临床医学院_心脏中心血管外科
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
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GB/T 7714
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.
APA Zhang, Xiangyu.,Zhang, Tao.,Gao, Fu.,Li, Qingle.,Shen, Chenyang.,...&Zhang, Xiaoming.(2015).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.MOLECULAR MEDICINE REPORTS,12(5),7317-7325.
MLA Zhang, Xiangyu,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".MOLECULAR MEDICINE REPORTS 12.5(2015):7317-7325.
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