title: Do multiple nuclear factor kappa B activation mechanisms explain its varied effects in the heart?
abstract: 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.
authors.affiliation: Division of Molecular Cardiology, College of Medicine, Texas A&M Health Science Center, Scott & White Healthcare, and Central Texas Veterans Health Care System, Temple, TX.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Qian Chen
authors.initials: QC
authors.lastname: Yong
authors.forename: Candice M
authors.initials: CM
authors.lastname: Thomas
keywords: Cytokines; NF-kappa B; diabetes mellitus; heart; renin-angiotensin system