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.
Cheng
J J
JJ
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
Chao
Y J
YJ
Wung
B S
BS
Wang
D L
DL
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008567:Membranes, Artificial; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000378:metabolism; D011312:Pressure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013314:Stress, Mechanical; D013997:Time Factors; D014470:Umbilical Cord
D000975:Antioxidants; D008567:Membranes, Artificial; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; D002374:Catalase; D000111:Acetylcysteine