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

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

Research output: Contribution to journalArticle

90 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number5 45-5
StatePublished - 1999

Fingerprint

Vascular Cell Adhesion Molecule-1
Endothelial cells
Shear flow
Monocytes
Adhesion
Endothelial Cells
Cell adhesion
Cell Adhesion
Chemical activation
Acetylcysteine
Cytokines
Oxidants
Flow patterns
Shear stress
Down-Regulation
Antioxidants
pyrrolidine dithiocarbamic acid

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion. / Mohan, Sumathy; Natarajan, Mohan; Valente, Anthony J.; Sprague, Eugene A.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 5 45-5, 1999.

Research output: Contribution to journalArticle

Mohan, Sumathy ; Natarajan, Mohan ; Valente, Anthony J. ; Sprague, Eugene A. / Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion. In: American Journal of Physiology - Cell Physiology. 1999 ; Vol. 276, No. 5 45-5.
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