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

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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 up...
Funding Information
  • National Institutes of Health (DK36118, EY01677, HL55477)

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