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学科主题: 临床医学
题名:
Matrix Metalloproteinase-8 Promotes Vascular Smooth Muscle Cell Proliferation and Neointima Formation
作者: Xiao, Qingzhong1; Zhang, Feng1,2; Grassia, Gianluca3; Hu, Yanhua4; Zhang, Zhongyi4; Xing, Qiuru4; Yin, Xiaoke4; Maddaluno, Marcella3; Drung, Binia5; Schmidt, Boris5; Maffia, Pasquale3,6; Ialenti, Armando3; Mayr, Manuel4; Xu, Qingbo4; Ye, Shu1
关键词: matrix metalloproteinase-8 ; myocytes, smooth muscle ; neointima
刊名: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
发表日期: 2014
DOI: 10.1161/ATVBAHA.113.301418
卷: 34, 期:1, 页:90-+
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Hematology ; Cardiovascular System & Cardiology
关键词[WOS]: LOW-DENSITY-LIPOPROTEIN ; N-CADHERIN CLEAVAGE ; ARTERIAL INJURY ; MIGRATION ; ADAM10 ; ATHEROSCLEROSIS ; DISINTEGRIN ; ADHESION ; PATHWAY ; HYPERPLASIA
英文摘要:

Objective-We investigated the role of matrix metalloproteinase-8 (MMP8) in neointima formation and in vascular smooth muscle cell (VSMC) migration and proliferation.

Approach and Results-After carotid artery wire injuring, MMP8(-/-)/apoE(-/-) mice had fewer proliferating cells in neointimal lesions and smaller lesion sizes. Ex vivo assays comparing VSMCs isolated from MMP8 knockout and wild-type mice showed that MMP8 knockout decreased proliferation and migration. Proteomics analysis revealed that a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) had lower concentrations in MMP8 knockout VSMC culture media than in MMP8 wild-type VSMC culture media. Western blot, flow cytometric, and immunocytochemical analyses showed that MMP8 knockout VSMCs contained more pro-ADAM10 but less mature ADAM10, more N-cadherin, and beta-catenin in the plasma membrane but less beta-catenin in the nucleus and less cyclin D1. Treatment of MMP8 wild-type VSMCs with an ADAM10 inhibitor, GI254023X, or siRNA knockdown of ADAM10 in MMP8 wild-type VSMCs inhibited proliferation and migration, increased N-cadherin and beta-catenin in the plasma membrane, reduced beta-catenin in the nucleus, and decreased cyclin D1 expression. Incubation of MMP8 knockout VSMCs with a recombinant ADAM10 rescued the proliferative and migratory ability of MMP8 knockout VSMCs and increased cyclin D1 expression. Furthermore, immunohistochemical analyses showed colocalization of ADAM10 with VSMCs and N-cadherin, and nuclear accumulation of beta-catenin in the neointima in apoE(-/-)/MMP8(+/+) mice.

Conclusions-MMP8 enhances VSMC proliferation via an ADAM10, N-cadherin, and beta-catenin-mediated pathway and plays an important role in neointima formation.

语种: 英语
所属项目编号: PG/08/051/25141 ; PG/11/40/28891 ; PG/13/45/30326 ; FS/11/28/28758 ; FS/09/044/28007 ; 2007LTAJMA_001
项目资助者: British Heart Foundation ; British Heart Foundation Intermediate Basic Science Research Fellowship ; Chinese Scholarship Council ; National Institute of Health Research ; Italian Government Grant PRIN
WOS记录号: WOS:000337731100014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59571
Appears in Collections:北京大学第二临床医学院_心血管内科_期刊论文

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作者单位: 1.Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England
2.Peking Univ, Peoples Hosp, Dept Cardiol, Beijing 100871, Peoples R China
3.Univ Naples Federico II, Dept Pharm, Naples, Italy
4.Kings Coll London, BHF Ctr, Cardiovasc Div, London, England
5.Tech Univ Darmstadt, Clemens Schopf Inst, Darmstadt, Germany
6.Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland

Recommended Citation:
Xiao, Qingzhong,Zhang, Feng,Grassia, Gianluca,et al. Matrix Metalloproteinase-8 Promotes Vascular Smooth Muscle Cell Proliferation and Neointima Formation[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2014,34(1):90-+.
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