Reactive oxygen species are involved in shear stress-induced intercellular adhesion molecule-1 expression in endothelial cells

J. J. Chiu, B. S. Wung, John Y.J. Shyy, H. J. Hsieh, D. L. Wang

Research output: Contribution to journalArticlepeer-review

155 Citations (Scopus)

Abstract

Vascular endothelial cells (ECs) are constantly subjected to flow- induced shear stress. Although the effects of shear stress on ECs are well known, the intracellular signal mechanisms remain largely unclear. Reactive oxygen species (ROS) have recently been suggested to act as intracellular second messengers. The potential role of ROS in shear-induced gene expression was examined in the present study by subjecting ECs to a shear force using a parallel-plate flow chamber system. ECs under shear flow increased their intracellular ROS as indicated by superoxide production. This superoxide production was maintained at an elevated level as shear flow remained. Sheared ECs, similar to TNF(α)-, PMA-, or H2O2-treated cells, increased their intercellular adhesion molecule-1 (ICAM-1) mRNA levels in a time- dependent manner. Pretreatment of ECs with an antioxidant, N-acetyl-cysteine (NAC) or catalase, inhibited this shear-induced or oxidant-induced ICAM-1 expression. ROS that were involved in the shear-induced ICAM-1 gene expression were further substantiated by functional analysis using a chimera containing the ICAM-1 promoter region (-850 bp) and the reporter gene luciferase. Shear-induced promoter activities were attenuated by pretreating sheared ECs with NAC and catalase. Flow cytometric analysis and monocytic adhesion assay confirmed the inhibitory effect of NAC and catalase on the shear-induced ICAM-1 expression on ECs. These results clearly demonstrate that shear flow to ECs can induce intracellular ROS generation that may result in an increase of ICAM-1 mRNA levels via transcriptional events. Our findings thus support the importance of intracellular ROS in modulating hemodynamically induced endothelial responses.

Original languageEnglish
Pages (from-to)3570-3577
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume17
Issue number12
DOIs
Publication statusPublished - Jan 1 1997
Externally publishedYes

Keywords

  • Endothelial cells
  • ICAM-1
  • Reactive oxygen species
  • Shear stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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