title: Mechanisms of persistent atrial fibrillation.
abstract: OBJECTIVE
  Atrial fibrillation is the most common sustained arrhythmia, but its mechanisms are poorly understood. In particular, little is known about the factors that contribute to the establishment of persistent or permanent atrial fibrillation. This review addresses possible common signaling pathways that might promote both structural and electrical remodeling of the atria, thus contributing to atrial fibrillation perpetuation.
  
  
  RESULTS
  Sustained atrial fibrillation may trigger an inflammatory response leading to activation of myofibroblasts and to the release of cytokines such as transforming growth factor-β and platelet-derived growth factor, as well as profibrotic proteins such as galectin-3. Activation of signaling cascades involving such proteins is critical for the development of fibrosis and may also lead to ion channel dysfunction, which, along with myocyte apoptosis and extracellular matrix generation and turnover, likely contributes to both electrical and structural remodeling and predisposes to atrial fibrillation.
  
  
  CONCLUSIONS
  Identifying upstream strategies targeting molecular pathways that are common to fibrosis and electrical remodeling leading to atrial fibrillation perpetuation is highly desirable. This would facilitate finding new target genes with pleiotropic effects on the expression of ion channel proteins in myocytes and profibrotic molecules in nonmyocyte cells that are important for pathologic remodeling, which could become an important goal in persistent atrial fibrillation therapy.
authors.affiliation: Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: José
authors.initials: J
authors.lastname: Jalife
mesh_terms: D017209:Apoptosis; D001281:Atrial Fibrillation / Q000276:immunology / Q000378:metabolism*; D064752:Atrial Remodeling / Q000276:immunology / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000276:immunology / Q000378:metabolism*; D037502:Galectin 3 / Q000276:immunology / Q000378:metabolism; D006325:Heart Atria / Q000276:immunology / Q000378:metabolism*; D006329:Heart Conduction System / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D058628:Myofibroblasts / Q000276:immunology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D037502:Galectin 3; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta