title: Multiple facets of NF-κB in the heart: to be or not to NF-κB.
abstract: The progression from cardiac injury to symptomatic heart failure has been intensely studied over the last decade, and is largely attributable to a loss of functional cardiac myocytes through necrosis, intrinsic and extrinsic apoptosis pathways and autophagy. Therefore, the molecular regulation of these cellular programs has been rigorously investigated in the hopes of identifying a potential cell target that could promote cell survival and/or inhibit cell death to avert, or at least prolong, the degeneration toward symptomatic heart failure. The nuclear factor (NF)-κB super family of transcription factors has been implicated in the regulation of immune cell maturation, cell survival, and inflammation in many cell types, including cardiac myocytes. Recent studies have shown that NF-κB is cardioprotective during acute hypoxia and reperfusion injury. However, prolonged activation of NF-κB appears to be detrimental and promotes heart failure by eliciting signals that trigger chronic inflammation through enhanced elaboration of cytokines including tumor necrosis factor α, interleukin-1, and interleukin-6, leading to endoplasmic reticulum stress responses and cell death. The underlying mechanisms that account for the multifaceted and differential outcomes of NF-κB on cardiac cell fate are presently unknown. Herein, we posit a novel paradigm in which the timing, duration of activation, and cellular context may explain mechanistically the differential outcomes of NF-κB signaling in the heart that may be essential for future development of novel therapeutic interventions designed to target NF-κB responses and heart failure following myocardial injury.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Gordon
authors.forename: James A
authors.initials: JA
authors.lastname: Shaw
authors.forename: Lorrie A
authors.initials: LA
authors.lastname: Kirshenbaum
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D009336:Necrosis
chemical_list: D016207:Cytokines; D016328:NF-kappa B