FLUID SHEAR-STRESS STIMULATES PLATELET-DERIVED GROWTH-FACTOR EXPRESSION IN ENDOTHELIAL-CELLS

Fluid flow and the associated shear stress play a critical role in vas cular growth and remodeling. Recent data suggest that increased endoth elial cell expression of platelet-derived growth factor (PDGF) A- and B-chain by flow may participate in these events. In the present study, we examined the mechanism for flow-induced PDGF expression, focusing on protein kinase C (PKC). Bovine aortic endothelial cells were expose d to flow (shear stress = 30 dyn/cm2) in a parallel-plate flow chamber . Increases in PDGF B-chain, but not PDGF A-chain, were observed withi n 3 h, maximal within 6 h (13-fold increase), and sustained for 24 h. PKC appeared to be involved because phorbol 12-myristate 13-acetate in duced PDGF B-chain mRNA. Activation of PKC alone, however, was insuffi cient to induce PDGF mRNA because the selective PKC activator, 1-oleoy l-2-acetyl-sn-glycerol, did not induce PDGF expression. A PKC-independ ent pathway was suggested by the fact that inhibition of PKC (downregu lation with phorbol 12,13-dibutyrate or exposure to staurosporine) fai led to block PMA or flow-induced PDGF B-chain expression. These result s demonstrate flow-induced PDGF B-chain expression in endothelial cell s that appears to be mediated, in part, by a PKC-independent pathway.