学科主题基础医学
Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2
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
2011-04-15
DOI10.1161/CIRCRESAHA.110.234328
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
WOS记录号WOS:000289510800006
项目编号81070243 ; 30870993 ; 30821001 ; B07001 ; 2010CB912504 ; 2011CB503904
资助机构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
引用统计
被引频次:38[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/400002259/67457
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.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
推荐引用方式
GB/T 7714
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.
APA Du, Yaoyao.,Wang, Yue.,Wang, Li.,Liu, Bo.,Tian, Qingyun.,...&Wang, Xian.(2011).Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2.CIRCULATION RESEARCH,108(8),917-U79.
MLA Du, Yaoyao,et al."Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2".CIRCULATION RESEARCH 108.8(2011):917-U79.
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