Cyclic strain-induced plasminogen activator inhibitor-1 (PAI-1) release from endothelial cells involves reactive oxygen species.

The molecular mechanisms of the endothelial fibrinolytic activities modulated by mechanical strain are not clear. Endothelial cells (ECs) grown on a flexible membrane base were deformed with sinusoidal negative pressures to produce an average strain of 12%. Cyclic strain induced PAI-1 release in a time-dependent manner. Strain cells resulted in a 5-fold increase in PAI-1 release. Strain induced a sustained elevated level in intracellular reactive oxygen species (ROS). Concomitantly, a sustained increase of catalase activity was observed. Both ROS and catalase activity returned to basal levels with the removal of strain. ECs pretreated with antioxidant, N-acetyl-cysteine, abolished the strain-induced ROS generation as well as strained-induced PAI-1 release. Our results indicate that cyclic strain-induced PAI-1 secretion may be mediated by an increase in ROS generation and thus emphasizes the importance of intracellular ROS in the modulation of hemodynamic force-induced cellular response of ECs.