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学科主题: 基础医学
题名:
Upregulation of a Disintegrin and Metalloproteinase With Thrombospondin Motifs-7 by miR-29 Repression Mediates Vascular Smooth Muscle Calcification
作者: Du, Yaoyao2; Gao, Cheng2; Liu, Ziyi2; Wang, Li2; Liu, Bo2; He, Fan3; Zhang, Tao4; Wang, Yue5; Wang, Xiujie; Xu, Mingjiang2; Luo, Guan-Zheng6; Zhu, Yi2; Xu, Qingbo7; Wang, Xian; Kong, Wei1,2
关键词: calcification ; smooth muscle cell ; protease ; microRNA ; animal model of human disease remodeling
刊名: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
发表日期: 2012-11-01
DOI: 10.1161/ATVBAHA.112.300206
卷: 32, 期:11, 页:2580-+
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]: CHRONIC KIDNEY-DISEASE ; OLIGOMERIC MATRIX PROTEIN ; ARTERIAL CALCIFICATION ; ANEURYSM DEVELOPMENT ; IN-VITRO ; PHOSPHATE ; CELLS ; MECHANISMS ; ROLES ; PATHOBIOLOGY
英文摘要:

Objective-Vascular calcification significantly increases cardiovascular morbidity and mortality. We recently reported that the deficiency of cartilage oligomeric matrix protein (COMP) leads to vascular mineralization. We characterized the COMP-degrading metalloproteinase, a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7). Here, we tested whether ADAMTS-7 facilitates vascular calcification.

Methods and Results-ADAMTS-7 expression was markedly upregulated in calcifying rat vascular smooth muscle cells (VSMCs) in vitro, calcified arteries of rats with chronic renal failure in vivo, and radial arteries of uraemic patients. Silencing of ADAMTS-7 markedly reduced COMP degradation and ameliorated VSMC calcification, whereas ectopic expression of ADAMTS-7 greatly enhanced COMP degradation and exacerbated mineralization. The transcriptional activity of ADAMTS-7 promoter was not altered by high phosphate. We used bioinformatics and quantitative polymerase chain reaction analysis to demonstrate that high-phosphate upregulated ADAMTS-7 mRNA and protein via miR-29a/b repression, which directly targeted the 3′ untranslated region of ADAMTS-7 in VSMCs. MicroRNA (MiR)-29a/b mimic markedly inhibited but miR-29a/b inhibitor greatly enhanced high-phosphate-induced ADAMTS-7 expression, COMP degradation, and subsequent VSMC calcification. ADAMTS-7 silencing significantly diminished miR-29a/b repression-exaggerated VSMC calcification.

Conclusion-Our data reveal a novel mechanism by which ADAMTS-7 upregulation by miR-29a/b repression mediates vascular calcification, which may shed light on preventing cardiovascular morbidity and mortality. (Arterioscler Thromb Vasc Biol. 2012;32:2580-2588.)

语种: 英语
所属项目编号: 81070243 ; 30870993 ; 81220108004 ; 81121061 ; 81170099 ; 2010 CB912504 ; 2012CB518002 ; B07001
项目资助者: National Natural Science Foundation of China ; National Program on Key Basic Research Project (973 Program) ; 111 Project of Chinese Ministry of Education
WOS记录号: WOS:000310058900010
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58504
Appears in Collections:基础医学院_生理学与病理生理学系_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
2.Peking Univ, Basic Med Coll, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Huazhong Univ Sci & Technol, Tongji Hosp, Div Nephrol, Wuhan 430074, Peoples R China
4.Chinese Peoples Liberat Army Gen Hosp, Dept Vasc Surg, Beijing, Peoples R China
5.Peking Univ, Hosp 3, Dept Nephrol, Beijing 100191, Peoples R China
6.Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China
7.Kings Coll London, BHF Ctr, Cardiovasc Div, London WC2R 2LS, England

Recommended Citation:
Du, Yaoyao,Gao, Cheng,Liu, Ziyi,et al. Upregulation of a Disintegrin and Metalloproteinase With Thrombospondin Motifs-7 by miR-29 Repression Mediates Vascular Smooth Muscle Calcification[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2012,32(11):2580-+.
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