Flow modulates endothelial regulation of smooth muscle cell proliferation: A new model

Background. With a co-culture model, we have previously demonstrated that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) behavior. ECs appeared to stimulate SMC proliferation in static culture. This study was performed to test the hypothesis that the EC stimulation of SMC proliferation wets effected by shear stress. Methods. Bovine SMCs were cultured on a thin semipermeable membrane either alone or opposite ECs in co-culture (SMC/EC). A novel parallel-plate flow device was developed and used for exposing the EC side of the co-culture to shear stress. EC and SMC proliferation rates were determined after 24 hours' exposure to 0, 1, or 10 dynes/cm(2) of shear stress, Results. SMC proliferation decreased significantly from 362 +/- 65 cpm/mu g DNA (control, mean +/- SEM) to 68 +/- 43 cpm/mu g (1 dyne/cm(2)) and 99 +/- 18 cpm/mu g (10 dynes/cm(2)) (P <. 05). EC proliferation after flow decreased as compared with no-flow controls 71 +/- 15 cpm/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 model designed to study SMC/EC interactions in a flow environment, it was seen that EC exposure to shear stress alters the growth characteristics of SMCs. This suggests that hemodynamic mechanical forces may be sufficient to alter the EC regulation of SMC behavior.