Mechanical stretch augments PDGF receptor beta expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells

With regard to the mechanotransduction mechanisms of vasculature involved i n hypertensive diseases, we aimed to identify tyrosine-phosphorylated prote ins in pulmonary artery that responded to mechanical stress. Mechanical str etch simultaneously augmented protein-tyrosine phosphorylation in p55, p95, p105, p115, p130, p165, p180 in pulmonary artery tissue and pulmonary arte ry-derived smooth muscle cells (PASMC), whereas p115 and p55 were preferent ially phosphorylated by the stretch in endothelial cells (PAEC). A series o f experiments designed to characterize these proteins indicated that p115 a nd p180 were focal adhesion kinase (FAK) and platelet-derived growth factor receptor beta (PDGF-R beta), respectively, and that stretch augmented the surface-expression of PDGF-R beta in PASMC but not in PAEC. Moreover, a sig nificant increase in the steady-state mRNA level for PDGF-R beta was observ ed in the pulmonary artery of rats with monocrotaline-induced pulmonary hyp ertension, where the artery should be overstretched due to increasing pulmo nary arterial blood pressure. These results suggest that stretch-induced ov erexpression of cell-surface PDGF-R beta as well as augmentation of tyrosin e phosphorylation of proteins including FAK in PASMC might be involved in t he mechanotransduction of pulmonary artery.