Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion

Sumathy Mohan, Natarajan Mohan, Anthony J. Valente, Eugene A. Sprague

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

We recently reported that prolonged exposure of human aortic endothelial cells (HAEC) to low shear stress flow patterns is associated with a sustained increase in the activated form of the transcriptional regulator nuclear factor-κB (NF-κB). Here we investigate the hypothesis that low shear- induced activation of NF-κB is responsible for enhanced expression of vascular cell adhesion molecule (VCAM-1) resulting in augmented endothelial cell-monocyte (EC-Mn) adhesion and that this activation is dependent on intracellular oxidant activity. Before exposure to low shear (2 dyn/cm2) for 6 h, HAEC were preincubated with or without the antioxidants pyrrolidine dithiocarbamate (PDTC) or N-acetyl-L-cysteine (NAC). PDTC strongly inhibited low shear-induced activation of NF-κB, expression of VCAM-1, and EC-Mn adhesion. Paradoxically, NAC exerted a positive effect on low shear-induced VCAM-1 expression and EC-Mn adhesion and only slightly downregulated NF-κB activation. However, cytokine-induced NF-κB activation and VCAM-1 expression are blocked by both PDTC and NAC. These data suggest that NF-κB plays a key role in low shear-induced VCAM-1 expression and that pathways mediating low shear- and cytokine-induced EC-Mn adhesion may be differentially regulated.

Original languageEnglish (US)
Pages (from-to)C1100-C1107
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number5 45-5
DOIs
StatePublished - 1999

Keywords

  • Atherosclerosis
  • Hemodynamics
  • Human aortic endothelial cell
  • Nuclear factor-κB
  • Transcription regulator
  • Vascular cell adhesion molecule

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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