Regulating the regulator: NF-κB signaling in heart

The Nuclear Factor-κB (NF-κB) signaling pathway has been linked to several pathologic processes in the myocardium including cardiomyocyte proinflammatory cytokine release, ischemia/reperfusion injury, hypertrophy and apoptosis. However, very little is known about the intracellular mechanisms that govern NF-κB activity in the myocardial cells. Recent advances in our understanding of the regulation of NF-κB signaling in non-myocyte systems suggest that the activity of the NF-κB pathway is tightly regulated by a diversity of stress-activated signaling intermediates through direct post-translational modification of various components of the NF-κB pathway. In this review, we will focus on these recent revelations and their implications not only in cardiac pathologies, but in the development of new therapeutic strategies to manage heart disease.