Role of the NF-kappaB signaling cascade and NF-kappaB-targeted genes in failing human hearts.

Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor that has been indicated to play a causal role for many pathological states. Heart failure is a major cause of morbidity all over the world. In this study, we examined the role of NF-kappaB in failing (F) human hearts and nonfailing (NF) controls. Our data showed that an enhanced activation of this nuclear factor occurs in the F hearts along with its components, like I-kappaB kinase (IKK)beta and IkappaBalpha, both at transcript and translational levels. To obtain a profile of NF-kappaB-targeted gene expression in F hearts, we profiled, for the first time, the expression analysis of NF-kappaB-linked gene using a TranSignal human NF-kappaB-targeted gene array. Our data suggest that more than 50 genes were consistently upregulated in F hearts more than 1.5-fold (vs NF hearts, p<0.001). Our studies demonstrated that NF-kappaB is specifically and significantly activated via IKKbeta in F hearts. The most intriguing aspects of our studies are molecular profiles of NF-kappaB-linked or targeted gene expression in F hearts. Our data suggest that the regulation and control of NF-kappaB activation is, therefore, a powerful therapeutic strategy for delaying or attenuating such deadly disease.