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学科主题: 基础医学
题名:
Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2
作者: Du, Yaoyao; Wang, Yue3; Wang, Li; Liu, Bo; Tian, Qingyun4,5; Liu, Chuan-Ju4,5; Zhang, Tao6; Xu, Qingbo7; Zhu, Yi; Oldberg, Ake8; Qi, Yongfen; Tang, Chaochu; Kong, Wei1; Wang, Xian
关键词: vascular smooth muscle cells ; calcification ; COMP ; BMP-2
刊名: CIRCULATION RESEARCH
发表日期: 2011-04-15
DOI: 10.1161/CIRCRESAHA.110.234328
卷: 108, 期:8, 页:917-U79
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Hematology
关键词[WOS]: CHRONIC KIDNEY-DISEASE ; CELLS ; MECHANISMS ; ARTERIES ; CALCIUM ; ADAMTS-7 ; AORTA ; ESRD
英文摘要:

Rationale: Vascular calcification is a significant contributor to cardiovascular morbidity and mortality. We recently reported that cartilage oligomeric matrix protein (COMP) is pivotal for maintaining the homeostasis of vascular smooth muscle cells (VSMCs). Whether COMP affects the process of vascular calcification is unknown.

Objective: We aimed to test whether COMP modulates vascular calcification.

Methods and Results: VSMC calcification in vitro was induced by calcifying media containing high inorganic phosphate or calcium. In vivo medial vessel calcification was induced in rats by 5/6 nephrectomy with a high-phosphate diet or by periadventitial application of CaCl2 to the abdominal aorta. COMP protein level was markedly reduced in both calcified VSMCs and arteries. COMP deficiency remarkably exacerbated VSMC calcification, whereas ectopic expression of COMP greatly reduced calcification. Furthermore, COMP knockdown facilitated osteogenic markers expression by VSMCs even in the absence of calcifying media. By contrast, COMP overexpression significantly inhibited high phosphate-or high calcium-induced VSMC osteochondrogenic transition. Induction of osteogenic marker expression by COMP silencing was reversed by a soluble form of bone morphogenetic protein (BMP)-2 receptor IA, which suggests a BMP-2-dependent mechanism. Our data revealed that COMP bound directly to BMP-2 through the C terminus, inhibited BMP-2 receptor binding, and blocked BMP-2 osteogenic signaling, indicating COMP inhibits osteochondrogenic transition of VSMCs at least partially through inhibiting BMP-2.

Conclusions: Our data strongly suggest that COMP is a novel inhibitor of vascular calcification. The imbalance between the effects of COMP and BMP-2 may provide new insights into the pathophysiology of vascular calcification. (Circ Res. 2011;108:917-928.)

语种: 英语
所属项目编号: 81070243 ; 30870993 ; 30821001 ; B07001 ; 2010CB912504 ; 2011CB503904
项目资助者: National Natural Science Foundation of the People&prime ; s Republic of China ; Ministry of Education of China ; 111 Project of China ; Major National Basic Research Grant of China
WOS记录号: WOS:000289510800006
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67457
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.Peking Univ, Dept Nephrol, Hosp 3, Beijing 100191, Peoples R China
4.NYU, Sch Med, Dept Orthopaed Surg, New York, NY 10003 USA
5.NYU, Sch Med, Dept Cell Biol, New York, NY 10003 USA
6.Peking Univ, Dept Vasc Surg, Peoples Hosp, Beijing 100191, Peoples R China
7.Kings Coll London, British Heart Fdn Ctr, Div Cardiovasc, London, England
8.Lund Univ, Biomed Ctr B12, Dept Cell & Mol Biol, S-22100 Lund, Sweden

Recommended Citation:
Du, Yaoyao,Wang, Yue,Wang, Li,et al. Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2[J]. CIRCULATION RESEARCH,2011,108(8):917-U79.
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