Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis
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Chunjiang Tan
Abstract
Background: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo.
Methods: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IκBα, phosphorylated IκB (pIκBα) and p65 were investigated by Western blotting or immunochemistry.
Results: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IκBα were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IκBα, and pIκBα were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups.
Conclusions: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IκBα and pIκBα, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.
Clin Chem Lab Med 2006;44:1218–25.
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©2006 by Walter de Gruyter Berlin New York
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