Stimulatory effect of ouabain on VCAM‐1 and iNOS expression in murine endothelial cells: involvement of NF‐κB

Abstract

Endothelial cells play a pivotal role in the development of atherosclerosis. An ‘activated’ phenotype of these cells is manifested by signal transduction-dependent expression of genes encoding cytokines, pro- and anticoagulant factors, and cell adhesion molecules. In the current study we examined the effect of ouabain, an inhibitor of Na⁺/K⁺-ATPase, on the process of endothelial cell activation. We demonstrated that ouabain was able to stimulate VCAM-1 expression and potentiate the effect of IFN-γ on this process. Moreover, ouabain provided a complementary signal for either TNF or IFN-γ in inducing iNOS expression. Our data also show, for the first time, that inhibition of Na⁺/K⁺-ATPase led to activation of the transcription factor, NF-κB, which may provide an explanation for the effects of ouabain on endothelial cells.