Cellular Biology Cartilage Oligomeric Matrix Protein Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells by Interacting With 71 Integrin

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 7 integrin coimmunoprecipitated with COMP in normal rat VSMCs and vessels, neutralizing antibody or siRNA against 7 integrin inhibited VSMC adhesion to COMP, which indicated that 71 integrin is a potential receptor for COMP. As well, blocking or interference by siRNA of 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 neointim