Contractility affects stress fiber remodeling and reorientation of endothelial cells subjected to cyclic mechanical stretching

We studied the effect of contractility on stress fiber remodeling and orien tation response of human aortic endothelial cells subjected to cyclic mecha nical stretching. The cells were grown on silicone membranes subjected to 1 0% cyclic pure uniaxial stretching in the presence or absence of 2,3 butane dione monoxime(BDM), a proven inhibitor of cellular contractility. It was f ound that treatment of the cells with BDM (40 mM) abolished stress fibers a nd blocked cell reorientation in response to cyclic stretching, indicating that contractility is required for these two cellular responses. When cells were stretched in the presence of N-acetylcysteine (NAC, 20 mM), a hydroge n peroxide (H2O2) scavenger, stress fibers were still formed and the cells reoriented-but more slowly. Specifically, compared with untreated cells, NA C treated cells after 0.5, 1, and 3 h of 10% stretching had significantly ( p<0.005) less skewed orientation distributions than those of untreated cell s. After the cells were treated with both NAC (20 mM) and nordihydroguaiare tic acid (NDGA, 50 <mu>M), another antioxidant, however, stress fibers were abolished and cell reorientation was completely blocked. These results ind icate that reactive oxygen species (ROS), including H2O2, affect stress fib er remodeling and reorientation of endothelial cells in response to cyclic stretching. We suggest that the effect of ROS on stress fiber remodeling an d cell reorientation is due to the ability of ROS to regulate cellular cont ractility, which is crucial for these cellular responses. (C) 2000 Biomedic al Engineering Society. [S0090-6964(00)001110-7].