Do multiple nuclear factor kappa B activation mechanisms explain its varied effects in the heart?

BACKGROUND: Multiple studies have demonstrated the important role of the nuclear factor kappa B (NF-κB) in cardiac pathology. However, these studies' conclusions differ regarding whether NF-κB is protective or detrimental for heart function. This disagreement is not surprising considering the complexity of NF-κB signaling that involves multiple components and regulation at several steps. Furthermore, NF-κB is a pleiotropic transcription factor that receives signals from multiple pathways, including the renin-angiotensin system (RAS) and cytokines, 2 important modulators of cardiac remodeling.
METHODS: In this article, we review studies related to the role and mechanisms of NF-κB activation in the heart, particularly with regard to the RAS, inflammation, and diabetes. The objective of this review is to consolidate multiple, often contradictory, findings to develop a clear understanding of NF-κB signaling in the heart.
CONCLUSIONS: The studies we review demonstrate that NF-κB effects in the heart are mechanism specific and that NF-κB signaling is cyclical. Consequently, the timing of NF-κB measurement is critical, and studies focused on temporal changes in the NF-κB mechanism would help clarify its multiple roles in cardiac pathophysiology.