Molecular mechanisms of atrial fibrosis: implications for the clinic

ABSTRACT

Introduction: 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.

KEYWORDS:

• Atrial fibrillation
• atrial fibrosis
• atrial remodeling
• molecular mechanisms
• risk factor management

Declaration of interest

P Sanders is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia; has served on the advisory board of Biosense-Webster, Medtronic, St Jude Medical, Boston Scientific and CathRx; has received lecture and/or consulting fees from Biosense-Webster, Medtronic, St Jude Medical, and Boston Scientific; has received research funding from Medtronic, St Jude Medical, Boston Scientific, Biotronik and Sorin. DH Lau has supported by the Robert J. Craig Lectureship from the University of Adelaide. T Agbaedeng is supported by the Peter M. Steele Postgraduate Scholarship from the University of Adelaide. A Elliott is supported by an Early Career Fellowship from the National Heart Foundation of Australia. R Mahajan is supported by an Early Career Fellowship jointly by the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia; and is supported by the Leo J. Mahar Lectureship from the University of Adelaide. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.