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Review

Are Interactions between Epicardial Adipose Tissue, Cardiac Fibroblasts and Cardiac Myocytes Instrumental in Atrial Fibrosis and Atrial Fibrillation?

by
Anirudh Krishnan
1,†,
Emily Chilton
2,†,
Jaishankar Raman
3,4,5,6,
Pankaj Saxena
7,
Craig McFarlane
8,
Alexandra F. Trollope
9,
Robert Kinobe
10 and
Lisa Chilton
10,*
1
College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia
2
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada
3
Austin & St Vincent’s Hospitals, Melbourne University, Melbourne, VIC 3010, Australia
4
Applied Artificial Intelligence Institute, Deakin University, Melbourne, VIC 3217, Australia
5
Department of Surgery, Oregon Health and Science University, Portland, OR 97239, USA
6
School of Engineering, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA
7
Department of Cardiothoracic Surgery, Townsville University Hospital, Townsville, QLD 4814, Australia
8
Centre for Tropical Bioinformatics and Molecular Biology, Australian Institute of Tropical Health and Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia
9
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia
10
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia
*
Author to whom correspondence should be addressed.
†
Anirudh Krishnan and Emily Chilton are co-first authors.
Cells 2021, 10(9), 2501; https://doi.org/10.3390/cells10092501
Submission received: 1 September 2021 / Revised: 12 September 2021 / Accepted: 14 September 2021 / Published: 21 September 2021
(This article belongs to the Special Issue Cardiac Fibroblasts, Fibrosis and Cardiovascular Disease)
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Abstract

Atrial fibrillation is very common among the elderly and/or obese. While myocardial fibrosis is associated with atrial fibrillation, the exact mechanisms within atrial myocytes and surrounding non-myocytes are not fully understood. This review considers the potential roles of myocardial fibroblasts and myofibroblasts in fibrosis and modulating myocyte electrophysiology through electrotonic interactions. Coupling with (myo)fibroblasts in vitro and in silico prolonged myocyte action potential duration and caused resting depolarization; an optogenetic study has verified in vivo that fibroblasts depolarized when coupled myocytes produced action potentials. This review also introduces another non-myocyte which may modulate both myocardial (myo)fibroblasts and myocytes: epicardial adipose tissue. Epicardial adipocytes are in intimate contact with myocytes and (myo)fibroblasts and may infiltrate the myocardium. Adipocytes secrete numerous adipokines which modulate (myo)fibroblast and myocyte physiology. These adipokines are protective in healthy hearts, preventing inflammation and fibrosis. However, adipokines secreted from adipocytes may switch to pro-inflammatory and pro-fibrotic, associated with reactive oxygen species generation. Pro-fibrotic adipokines stimulate myofibroblast differentiation, causing pronounced fibrosis in the epicardial adipose tissue and the myocardium. Adipose tissue also influences myocyte electrophysiology, via the adipokines and/or through electrotonic interactions. Deeper understanding of the interactions between myocytes and non-myocytes is important to understand and manage atrial fibrillation.
Keywords: myofibroblast; adipokine; electrotonic coupling; current sink myofibroblast; adipokine; electrotonic coupling; current sink

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MDPI and ACS Style

Krishnan, A.; Chilton, E.; Raman, J.; Saxena, P.; McFarlane, C.; Trollope, A.F.; Kinobe, R.; Chilton, L. Are Interactions between Epicardial Adipose Tissue, Cardiac Fibroblasts and Cardiac Myocytes Instrumental in Atrial Fibrosis and Atrial Fibrillation? Cells 2021, 10, 2501. https://doi.org/10.3390/cells10092501

AMA Style

Krishnan A, Chilton E, Raman J, Saxena P, McFarlane C, Trollope AF, Kinobe R, Chilton L. Are Interactions between Epicardial Adipose Tissue, Cardiac Fibroblasts and Cardiac Myocytes Instrumental in Atrial Fibrosis and Atrial Fibrillation? Cells. 2021; 10(9):2501. https://doi.org/10.3390/cells10092501

Chicago/Turabian Style

Krishnan, Anirudh, Emily Chilton, Jaishankar Raman, Pankaj Saxena, Craig McFarlane, Alexandra F. Trollope, Robert Kinobe, and Lisa Chilton. 2021. "Are Interactions between Epicardial Adipose Tissue, Cardiac Fibroblasts and Cardiac Myocytes Instrumental in Atrial Fibrosis and Atrial Fibrillation?" Cells 10, no. 9: 2501. https://doi.org/10.3390/cells10092501

APA Style

Krishnan, A., Chilton, E., Raman, J., Saxena, P., McFarlane, C., Trollope, A. F., Kinobe, R., & Chilton, L. (2021). Are Interactions between Epicardial Adipose Tissue, Cardiac Fibroblasts and Cardiac Myocytes Instrumental in Atrial Fibrosis and Atrial Fibrillation? Cells, 10(9), 2501. https://doi.org/10.3390/cells10092501

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