title: Molecular mechanisms of atrial fibrosis: implications for the clinic.
abstract: Recent research has unravelled an increasing list of cardiac conditions and risk factors that may be responsible for the abnormal underlying atrial substrate that predisposes to atrial fibrillation (AF). Atrial fibrosis has been demonstrated as the pivotal structural abnormality underpinning conduction disturbances that promote AF in different disease models. Despite the advancement in our discoveries of the molecular mechanisms involved in the profibrotic milieu, targeted therapeutics against atrial fibrosis remain lacking. Areas covered: This review is focused on detailing the key molecular signalling pathways that contribute to atrial fibrosis including: angiotensin II, transforming growth factor (TGF- ß1), connective tissue growth factor (CTGF) and endothelin-1. We also discussed the potential therapeutic options that may be useful in modulating the abnormal atrial substrate. In addition, we examined the new paradigm of AF care in lifestyle and risk factor management that has been shown to arrest and reverse the atrial remodelling process leading to improved AF outcomes. Expert commentary: The future of AF care is likely to require an integrated approach consisting of aggressive risk factor management in addition to the established paradigm of rate and rhythm management and anticoagulation. Translational studies on molecular therapeutics to combat atrial fibrosis is urgently needed.
authors.affiliation: a Centre for Heart Rhythm Disorders , South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital , Adelaide , Australia.
authors.forename: Shivshankar
authors.initials: S
authors.lastname: Thanigaimani
authors.affiliation: a Centre for Heart Rhythm Disorders , South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital , Adelaide , Australia.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Lau
authors.affiliation: a Centre for Heart Rhythm Disorders , South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital , Adelaide , Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Agbaedeng
authors.affiliation: a Centre for Heart Rhythm Disorders , South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital , Adelaide , Australia.
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Elliott
authors.affiliation: a Centre for Heart Rhythm Disorders , South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital , Adelaide , Australia.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Mahajan
authors.affiliation: a Centre for Heart Rhythm Disorders , South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital , Adelaide , Australia.
authors.forename: Prashanthan
authors.initials: P
authors.lastname: Sanders
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D001281:Atrial Fibrillation / Q000628:therapy*; D005355:Fibrosis / Q000473:pathology; D006325:Heart Atria / Q000503:physiopathology*; D006801:Humans; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D000804:Angiotensin II
keywords: Atrial fibrillation; atrial fibrosis; atrial remodeling; molecular mechanisms; risk factor management