Cartilage oligomeric matrix protein maintains the contractile phenotype of vascular smooth muscle cells by interacting with alpha(7)beta(1) integrin.
BACKGROUND
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.


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.
Wang
Li
L
Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing 100191, People's Republic of China.
Zheng
Jingang
J
Du
Yaoyao
Y
Huang
Yaqian
Y
Li
Jing
J
Liu
Bo
B
Liu
Chuan-ju
CJ
Zhu
Yi
Y
Gao
Yuansheng
Y
Xu
Qingbo
Q
Kong
Wei
W
Wang
Xian
X
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001013:Aorta, Thoracic / Q000166:cytology; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism*; D002404:Catheterization / Q000009:adverse effects; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006023:Glycoproteins / Q000502:physiology*; D039001:Integrin alpha Chains / Q000037:antagonists & inhibitors / Q000235:genetics; D016023:Integrins / Q000737:chemistry / Q000502:physiology*; D008297:Male; D064235:Matrilin Proteins; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D025941:Protein Interaction Mapping; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000502:physiology
D015703:Antigens, CD; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D039001:Integrin alpha Chains; D016023:Integrins; D064235:Matrilin Proteins; D009124:Muscle Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C085725:integrin alpha7; D000077214:Becaplermin; C082908:integrin alpha7beta1