学科主题基础医学
Cartilage Oligomeric Matrix Protein Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells by Interacting With alpha(7)beta(1) Integrin
Wang, Li1; Zheng, Jingang3; Du, Yaoyao1; Huang, Yaqian1; Li, Jing1; Liu, Bo1; Liu, Chuan-ju4,5; Zhu, Yi1; Gao, Yuansheng1; Xu, Qingbo6; Kong, Wei1; Wang, Xian1
关键词smooth muscle cells phenotype COMP integrin neointima
刊名CIRCULATION RESEARCH
2010-02-19
DOI10.1161/CIRCRESAHA.109.202762
106期:3页:514-525
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]EXPRESSION ; ADHESION ; DIFFERENTIATION ; MODULATION ; ACTIN ; ATHEROSCLEROSIS ; TRANSDUCTION ; MAINTENANCE ; MYOCARDIN ; DYNAMICS
英文摘要

Rational: Vascular smooth muscle cells (VSMCs) switching from a contractile/differentiated to a synthetic/dedifferentiated phenotype has an essential role in atherosclerosis, postangioplastic restenosis and hypertension. However, how normal VSMCs maintain the differentiated state is less understood.

Objective: We aimed to indentify the effect of cartilage oligomeric matrix protein (COMP), a normal vascular extracellular matrix, on modulation of VSMCs phenotype.

Methods and Results: We demonstrated that COMP was associated positively with the expression of VSMC differentiation marker genes during phenotype transition. Knockdown of COMP by small interfering (si) RNA favored dedifferentiation. Conversely, adenoviral overexpression of COMP markedly suppressed platelet-derived growth factor-BB-elicited VSMC dedifferentiation, characterized by altered VSMC morphology, actin fiber organization, focal adhesion assembly, and the expression of phenotype-dependent markers. Whereas alpha(7) integrin coimmunoprecipitated with COMP in normal rat VSMCs and vessels, neutralizing antibody or siRNA against alpha(7) integrin inhibited VSMC adhesion to COMP, which indicated that alpha(7)beta(1) integrin is a potential receptor for COMP. As well, blocking or interference by siRNA of alpha(7) integrin completely abolished the effect of COMP on conserving the contractile phenotype. In accordance, ectopic adenoviral overexpression of COMP greatly retarded VSMC phenotype switching, rescued contractility of carotid artery ring, and inhibited neointima formation in balloon-injured rats.

Conclusions: Our data suggest that COMP is essential for maintaining a VSMC contractile phenotype and the protective effects of COMP are mainly mediated through interaction with alpha(7)beta(1) integrin. Investigations to identify the factors affecting the expression and integrity of COMP may provide a novel therapeutic target for vascular disorders. (Circ Res. 2010;106:514-525.)

语种英语
WOS记录号WOS:000274651400014
项目编号30670849 ; 30870993 ; 30821001 ; 30770865 ; 2006CB503802 ; 307001
资助机构National Natural Science Foundation of the People&prime ; s Republic of China ; Natural Science Foundation of Beijing ; Ministry of Education of China ; Chinese Ministry of Education ; Chang Jiang Scholars Program
引用统计
被引频次:55[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/400002259/51781
专题北京大学基础医学院_生理学与病理生理学系
作者单位1.NYU, Sch Med, Dept Cell Biol, New York, NY 10003 USA
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
3.NYU, Sch Med, Dept Orthopaed Surg, New York, NY 10003 USA
4.Peking Univ, Basic Med Coll, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China
5.China Japan Friendship Hosp, Dept Cardiol, Beijing, Peoples R China
6.Kings Coll London, British Heart Fdn Ctr, Div Cardiovasc, London, England
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GB/T 7714
Wang, Li,Zheng, Jingang,Du, Yaoyao,et al. Cartilage Oligomeric Matrix Protein Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells by Interacting With alpha(7)beta(1) Integrin[J]. CIRCULATION RESEARCH,2010,106(3):514-525.
APA Wang, Li.,Zheng, Jingang.,Du, Yaoyao.,Huang, Yaqian.,Li, Jing.,...&Wang, Xian.(2010).Cartilage Oligomeric Matrix Protein Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells by Interacting With alpha(7)beta(1) Integrin.CIRCULATION RESEARCH,106(3),514-525.
MLA Wang, Li,et al."Cartilage Oligomeric Matrix Protein Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells by Interacting With alpha(7)beta(1) Integrin".CIRCULATION RESEARCH 106.3(2010):514-525.
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