Phenotype dictates the growth response of vascular smooth muscle cells to pulse pressure in vitro

The objective of this study was to determine the effect of phenotype on pul se pressure-induced signaling and growth of vascular smooth muscle cells in vitro. Using a perfused transcapillary culture system, cells were exposed to increases in pulsatile flow and hence pulse pressure and maintained for 72 h before cells were harvested. Cell proliferation was determined by cell number, DNA synthesis, and proliferating cell nuclear antigen expression. Mitogen-activated protein kinase (MAPK) levels were determined by immunoblo t and kinase activity by phosphorylation of myelin basic protein. Cell phen otype was determined by immunoblot and immunocytofluorescence using antiser a specific for the differentiation markers alpha-actin, myosin, calponin, o steopontin, and phospholamban. In cells that highly expressed these differe ntiation markers, there was a significant increase in cell growth in respon se to chronic increases in pulse pressure without a significant change in M APK activity in these cells. In contrast, in cells that weakly expressed SM C differentiation markers, there was a significant decrease in cell growth concomitant with a significant decrease in MAPK signaling in these cells. W e conclude that SMC phenotype dictates the growth response of SMC to mechan ical force in vitro. (C) 1999 Academic Press.