Cellular and mitochondrial mechanisms of atrial fibrillation
- PDF / 1,872,142 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 4 Downloads / 199 Views
REVIEW
Cellular and mitochondrial mechanisms of atrial fibrillation Fleur E. Mason1,2 · Julius Ryan D. Pronto1,2 · Khaled Alhussini3 · Christoph Maack4,5 · Niels Voigt1,2,6 Received: 13 May 2020 / Accepted: 26 October 2020 © The Author(s) 2020
Abstract The molecular mechanisms underlying atrial fibrillation (AF), the most common form of arrhythmia, are poorly understood and therefore target-specific treatment options remain an unmet clinical need. Excitation–contraction coupling in cardiac myocytes requires high amounts of adenosine triphosphate (ATP), which is replenished by oxidative phosphorylation in mitochondria. Calcium (Ca2+) is a key regulator of mitochondrial function by stimulating the Krebs cycle, which produces nicotinamide adenine dinucleotide for ATP production at the electron transport chain and nicotinamide adenine dinucleotide phosphate for the elimination of reactive oxygen species (ROS). While it is now well established that mitochondrial dysfunction plays an important role in the pathophysiology of heart failure, this has been less investigated in atrial myocytes in AF. Considering the high prevalence of AF, investigating the role of mitochondria in this disease may guide the path towards new therapeutic targets. In this review, we discuss the importance of mitochondrial Ca2+ handling in regulating ATP production and mitochondrial ROS emission and how alterations, particularly in these aspects of mitochondrial activity, may play a role in AF. In addition to describing research advances, we highlight areas in which further studies are required to elucidate the role of mitochondria in AF. Keywords Atrial fibrillation · Mitochondria · Electrophysiology · Oxidative stress · Calcium · Atrial cardiomyopathy
Introduction Atrial fibrillation (AF) is the most common sustained arrhythmia and causes substantial morbidity and mortality, particularly due to embolic stroke [5, 88]. Currently Fleur E. Mason and Julius Ryan D. Pronto contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00395-020-00827-7) contains supplementary material, which is available to authorized users. * Christoph Maack [email protected] * Niels Voigt [email protected]‑goettingen.de 1
Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University Göttingen, Robert‑Koch‑Straße 40, 37075 Göttingen, Germany
2
DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
3
Department of Thoracic and Cardiovascular Surgery, University Clinic Würzburg, Würzburg, Germany
available AF therapies have limited efficacy and safety, particularly in patients with long-standing persistent (‘chronic’) AF (cAF). A greater understanding of the molecular mechanisms promoting AF is expected to facilitate the development of improved and better-targeted anti-AF therapies [33, 48]. The underlying mechanisms initiating and promoting AF are incompletely resolved [81]. However, calcium (Ca2+) h
Data Loading...
