FLOW MODULATES ENDOTHELIAL REGULATION OF SMOOTH-MUSCLE CELL-PROLIFERATION - A NEW MODEL

Background. With a co-culture model, we have previously demonstrated t hat endothelial cells (ECs) exert regulatory control over smooth muscl e cell (SMC) behavior. ECs appeared to stimulate SMC proliferation in static culture. This study was performed to test the hypothesis that t he EC stimulation of SMC proliferation wets effected by shear stress. Methods. Bovine SMCs were cultured on a thin semipermeable membrane ei ther alone or opposite ECs in co-culture (SMC/EC). A novel parallel-pl ate flow device was developed and used for exposing the EC side of the co-culture to shear stress. EC and SMC proliferation rates were deter mined after 24 hours' exposure to 0, 1, or 10 dynes/cm(2) of shear str ess, Results. SMC proliferation decreased significantly from 362 +/- 6 5 cpm/mu g DNA (control, mean +/- SEM) to 68 +/- 43 cpm/mu g (1 dyne/c m(2)) and 99 +/- 18 cpm/mu g (10 dynes/cm(2)) (P <. 05). EC proliferat ion after flow decreased as compared with no-flow controls 71 +/- 15 c pm/mu g DNA (control, mean +/- SEM) to 29 +/- 5 cpm/mu g (1 dyne/cm(2) ) and 21 +/- 4 cpm/mu g (10 dynes/cm(2)) (P <.05). Conclusions. In a m odel designed to study SMC/EC interactions in a flow environment, it w as seen that EC exposure to shear stress alters the growth characteris tics of SMCs. This suggests that hemodynamic mechanical forces may be sufficient to alter the EC regulation of SMC behavior.