学科主题基础医学
Upregulation of a Disintegrin and Metalloproteinase With Thrombospondin Motifs-7 by miR-29 Repression Mediates Vascular Smooth Muscle Calcification
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
2012-11-01
DOI10.1161/ATVBAHA.112.300206
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
WOS记录号WOS:000310058900010
项目编号81070243 ; 30870993 ; 81220108004 ; 81121061 ; 81170099 ; 2010 CB912504 ; 2012CB518002 ; B07001
资助机构National Natural Science Foundation of China ; National Program on Key Basic Research Project (973 Program) ; 111 Project of Chinese Ministry of Education
引用统计
被引频次:46[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58504
专题北京大学基础医学院_生理学与病理生理学系
北京大学基础医学院
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
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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-+.
APA Du, Yaoyao.,Gao, Cheng.,Liu, Ziyi.,Wang, Li.,Liu, Bo.,...&Kong, Wei.(2012).Upregulation of a Disintegrin and Metalloproteinase With Thrombospondin Motifs-7 by miR-29 Repression Mediates Vascular Smooth Muscle Calcification.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,32(11),2580-+.
MLA Du, Yaoyao,et al."Upregulation of a Disintegrin and Metalloproteinase With Thrombospondin Motifs-7 by miR-29 Repression Mediates Vascular Smooth Muscle Calcification".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 32.11(2012):2580-+.
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