title: Cyclic strain-induced reactive oxygen species involved in ICAM-1 gene induction in endothelial cells.
abstract: Vascular endothelial cells (ECs) are constantly subjected to pressure-induced strain. We have previously demonstrated that strain can induce intercellular adhesion molecule-1 (ICAM-1) expression in ECs. The molecular mechanisms of gene induction by strain, however, remain unclear. Recent evidence suggests that intracellular reactive oxygen species (ROS) may act as second messengers. The potential role of ROS in strain-induced ICAM-1 expression was examined. ECs grown on a flexible membrane base were deformed with various sinusoidal negative pressures to produce an average strain of 12%. Cyclic strain induced an increase in intracellular ROS measured by fluorescent intensity of dichlorofluorescein formed after peroxidation. Maximal levels of ROS were seen after 30 minutes. Levels subsequently decreased but remained elevated compared with unstrained groups. Concomitantly, a sustained increase of H2O2 decomposition activity was observed in strained ECs. Both ROS and H2O2 decomposition activity returned to basal levels after removal of the strain. ECs treated with an antioxidant (N-acetylcysteine or catalase) inhibited strain-induced ROS generation and ICAM-1 mRNA levels followed by decreased ICAM-1 expression on EC surfaces. This inhibition may account for the reduced monocytic cell adhesion in antioxidant-treated ECs but not in strained controls. Our findings indicate that cyclic strain-induced monocyte adhesion to ECs is mediated, at least in part, by an increase of ICAM-1 gene expression via the elevation of ROS levels in strained ECs. Our results support the importance of intracellular ROS in the modulation of hemodynamic force-induced endothelial responses.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cheng
authors.forename: B S
authors.initials: BS
authors.lastname: Wung
authors.forename: Y J
authors.initials: YJ
authors.lastname: Chao
authors.forename: D L
authors.initials: DL
authors.lastname: Wang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D018056:Hemorheology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1