Role And Mechanism Of Integrin On Mechanical Stress-induced Arterial Remodeling

Arterial remodeling is the important pathological characteristics of cardiovascular diseases such as hypertension, however, the role and mechanism of hemodynamic factors on arterial remodeling has not been understood well yet. To investigate the effect of pure mechanical stress on arterial remodeling, a new model of common carotid artery exposing to stress in vivo was established in rat. Using this model, the following experiments were performed. The effect of high perfusingand immnohistochemistry. The expressions and distributions of integrin p3, paxillin and vinculin, as well as the expressions of c-Jun, c-Fos, phospho-ERK, phosphotyrosine and c-fos mRNA were studied by immunohistochemistry, immunoelectromicroscopy, and in situ hybridization. Effects of ROD peptides, an integrin competitive inhibitor, on the expressions of phospho-ERK, and phosphotyrosine and c-fos were determined also by immunohistochemistry and in situ hybridization. High pressure increased the euchromatin in nucleus of VSMC, but reduced the expression of a-actin. There were PCNA-positive particles in VSMC. Integrin fc, paxillin and vinculin were located in VSMC cytoplasm and membrane, and redistributed VSMC membrane under high pressure. The expression of paxillin increased after 30 min high pressure perfusing, but decreased 6 hours latter. The expression of c-Jun was detected in VSMC at 30 min in high pressure group and positive related to perfusing time, while it was detected 1 hour latter that in normal pressure group. The c-Fos expressed only in high pressure group 6 hours latter. The expressions of phospha-ERK, phosphotyrosine and c-fosmRNA in VSMC increased in high pressure group, but were inhibited by ROD peptide. These results suggest that high pressure promotes VSMC in common carotid artery of rat to change into synthetic phenotype from contractile phenotype, and tends to growth under influence of the high pressure. The high pressure induced the aggregation of integrin f33, paxillin and vinculin, and activated the phosphorylation of ERK and tyrosine, and promoted the expression of c-Jun, c-Fos, and c-fos mRNA. ROD peptide inhibited the above effects of high pressure. The study demonstrates that paxillin, vinculin, ERK, tyrosine, c-Jun and c-Fos take part in the mechnotransduction of VSMC via integrin, and play important roles on arterial remodeling induced by mechanical stress.