Vacuolar H+-ATPase plays a crucial role in growth and phenotypic modulation of myofibroblasts in cultured human saphenous vein

Background-The molecular mechanism of neointimal hyperplasia after vein gra ft surgery remains elusive. Vacuolar H+-ATPase (V-ATPase) is involved in in tracellular trafficking and may play a crucial role in neointimal cell grow th. Methods mid Results-Cultured human saphenous vein segments developed neoint imal formation within 10 days. Neointimal cells were positive for vimentin and alpha -smooth muscle actin but negative for desmin, which is indicative of myofibroblasts, Those myofibroblasts were found to have originated from periadventitial fibroblasts, which upregulated the expression of 16-kDa pr oteolipid of V-ATPase before proliferation and phenotypic modulation. Neoin timal myofibroblast growth and survival were highly sensitive to inhibition of V-ATPase by bafilomycin A(1) (BA(1)), because the incorporation of [H-3 ]thymidine into the myofibroblasts was significantly inhibited by nanomolar concentrations of BA(1) and apoptotic cell death was induced by a similar concentration range of BA(1). In contrast, endothelial cells and differenti ated smooth muscle cells were resistant to apoptosis by BA(1). Conclusions-These results suggest that V-ATPase plays a crucial role in gro wth and phenotypic modulation of myofibroblasts that contributes to neointi mal formation in cultured human saphenous vein.