title: TNF revisited: osteoprotegerin and TNF-related molecules in heart failure.
abstract: The pathophysiological role of tumor necrosis factor (TNF) in myocardial failure has been extensively examined in experimental and clinical studies. Recent studies suggest that other members of the TNF/TNF receptor superfamily (TNFSF/TNFRSF) also may play a pathogenic role in chronic HF. TNF ligands, and in particular members of the TNFRSF, are expressed by a wide variety of cells, including myocardial cells. By activating the nuclear factor-κB (NF-κB) and death-related pathways, TNF ligands can induce a variety of effects within the myocardium, including apoptosis, hypertrophy, inflammation, and extracellular matrix remodeling. Among several TNFSF members that have been shown activated in HF, the OPG/RANK/RANKL (osteoprotegerin/receptor activator of NF-κB/RANK ligand) axis may be of importance in the pathogenesis of this disorder through different mechanisms. In this paper, we revisited the role of TNFSF/TNFRSF in the pathophysiology of HF, possibly representing new targets for therapy as well as new biomarkers in this disorder.
authors.affiliation: Research Institute of Internal Medicine, Faculty of Medicine, Rikshospitalet, Oslo University Hospital, Sognsvannsveien 20, 0027, Oslo, Norway. thor.ueland@medisin.uio.no
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D005109:Extracellular Matrix / Q000502:physiology; D006333:Heart Failure / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008024:Ligands; D053244:Osteoprotegerin / Q000502:physiology*; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D015415:Biomarkers; D008024:Ligands; D053244:Osteoprotegerin; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha