Inhibition of aldose reductase attenuates TNF-α-induced expression of adhesion molecules in endothelial cells

Kota Ramana, Aruni Bhatnagar, Satish Srivastava

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Increased expression of adhesion molecules by the activated endothelium is a critical feature of vascular inflammation associated with several disease states such as atherosclerosis. However, mechanisms regulating the endothelial induction of adhesion molecules are not entirely clear. Herein we report that inhibition of the polyol pathway enzyme aldose reductase (AR) prevents the increase in ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVECs) and decreases monocyte adhesion to these cells. In TNF-α-stimulated HUVECs, treatment with AR inhibitors sorbinil and tolrestat diminished NF-κB activity, phosphorylation and degradation of Iκ-Bα, and the nuclear translocation of NF-κB. Inhibition of AR abrogated TNF-α-induced activation and membrane translocation of PKC, and antisense ablation of AR prevented both TNF-α-induced PKC and NF-κB activation. However, inhibition of AR did not prevent phorbol ester-induced activation of PKC or NF-κB, indicating that inhibition of AR does prevents events upstream of PKC activation. These results identify a novel regulator of endothelial activation and suggest that AR is an obligatory mediator of TNF-α signaling leading to an increase in the expression of adhesion molecules and increased binding of monocytes to the endothelium.

Original languageEnglish (US)
Pages (from-to)1209-1218
Number of pages10
JournalFASEB Journal
Volume18
Issue number11
DOIs
StatePublished - Aug 2004

Fingerprint

aldehyde reductase
Aldehyde Reductase
Endothelial cells
endothelial cells
adhesion
Adhesion
Endothelial Cells
Molecules
Chemical activation
Human Umbilical Vein Endothelial Cells
endothelium
monocytes
Endothelium
Monocytes
Phosphorylation
polyols
Vascular Cell Adhesion Molecule-1
Phorbol Esters
Intercellular Adhesion Molecule-1
Ablation

Keywords

  • Monocyte and adhesion molecules
  • NF-κB
  • PKC activity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Inhibition of aldose reductase attenuates TNF-α-induced expression of adhesion molecules in endothelial cells. / Ramana, Kota; Bhatnagar, Aruni; Srivastava, Satish.

In: FASEB Journal, Vol. 18, No. 11, 08.2004, p. 1209-1218.

Research output: Contribution to journalArticle

Ramana, Kota ; Bhatnagar, Aruni ; Srivastava, Satish. / Inhibition of aldose reductase attenuates TNF-α-induced expression of adhesion molecules in endothelial cells. In: FASEB Journal. 2004 ; Vol. 18, No. 11. pp. 1209-1218.
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