Recent advances in the molecular pathophysiology of atrial fibrillation
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TLDR
The ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia are discussed, including the potential therapeutic implications that might arise from an improved mechanistic understanding.Abstract:
Atrial fibrillation (AF) is an extremely common cardiac rhythm disorder that causes substantial morbidity and contributes to mortality. The mechanisms underlying AF are complex, involving both increased spontaneous ectopic firing of atrial cells and impulse reentry through atrial tissue. Over the past ten years, there has been enormous progress in understanding the underlying molecular pathobiology. This article reviews the basic mechanisms and molecular processes causing AF. We discuss the ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia. We conclude with a discussion of the potential therapeutic implications that might arise from an improved mechanistic understanding.read more
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Journal ArticleDOI
Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm.
Natalia Smorodinova,Martin Bláha,Vojtěch Melenovský,Karolína Rozsívalová,Jaromír Přidal,Mária Ďurišová,Jan Pirk,Josef Kautzner,Tomáš Kučera +8 more
TL;DR: An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage.
Journal ArticleDOI
Prediction of atrial fibrillation development and progression: Current perspectives.
Konstantinos Vlachos,Konstantinos P. Letsas,Panagiotis Korantzopoulos,Tong Liu,Stamatis Georgopoulos,Athanasios Bakalakos,Nikolaos Karamichalakis,Sotirios Xydonas,Michael Efremidis,Antonios Sideris +9 more
TL;DR: There is now increasing evidence that even in patients with so-called lone or idiopathic AF, the arrhythmia is the manifestation of a structural atrial disease which has recently been defined and described as fibrotic atrial cardiomyopathy.
Journal ArticleDOI
Loss of Nav1.5 expression and function in murine atria containing the RyR2-P2328S gain-of-function mutation
James King,Chandu Wickramarachchi,Krystine Kua,Yuan Du,Kamalan Jeevaratnam,Hugh R. Matthews,Andrew A. Grace,Christopher L.-H. Huang,James A. Fraser +8 more
TL;DR: The results suggest that raised [Ca(2+)]i produces both acute and chronic inhibition of Na(+) channel function, which may help explain the relationship between altered Ca(2+) homeostasis, CV, and the maintenance of common arrhythmias such as atrial fibrillation.
Journal ArticleDOI
Dysfunction of Myosin Light-Chain 4 (MYL4) Leads to Heritable Atrial Cardiomyopathy With Electrical, Contractile, and Structural Components: Evidence From Genetically-Engineered Rats
Wenhui Peng,Miaoxin Li,Hailing Li,Kai Tang,Jianhui Zhuang,Jianguo Zhang,Jingjing Xiao,Hui Jiang,Dali Li,Yongchun Yu,Pak C. Sham,Stanley Nattel,Yawei Xu +12 more
TL;DR: These results improve the understanding of the molecular basis of atrial cardiomyopathy and introduce new models for further mechanistic analysis, identifying MYL4 as a key gene required for atrial contractile, electrical and structural integrity.
Journal ArticleDOI
Chronic atrial fibrillation up-regulates β1-Adrenoceptors affecting repolarizing currents and action potential duration
Marta González de la Fuente,Adriana Barana,Ricardo Gómez,Irene Amorós,Pablo Dolz-Gaitón,Sandra Sacristán,Felipe Atienza,Ana Pita,Ángel González Pinto,Francisco Fernández-Avilés,Ricardo Caballero,Juan Tamargo,Eva Delpón +12 more
TL;DR: It is demonstrated that CAF increases the effects of β1-Adrenoceptor stimulation on repolarizing currents by means of a chamber-specific up-regulation of the receptors, which could contribute to the long-term stabilization of the arrhythmia by shortening the AP duration.
References
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Journal ArticleDOI
Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins
Michel Haïssaguerre,Pierre Jaïs,D. C. Shah,Atsushi Takahashi,Mélèze Hocini,G Quiniou,S. Garrigue,A Le Mouroux,P Le Métayer,Jacques Clementy +9 more
TL;DR: The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation and these foci respond to treatment with radio-frequency ablation.
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Atrial Fibrillation Begets Atrial Fibrillation A Study in Awake Chronically Instrumented Goats
TL;DR: Artificial maintenance of AF leads to a marked shortening of AERP, a reversion of its physiological rate adaptation, and an increase in rate, inducibility and stability of AF.
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Secular Trends in Incidence of Atrial Fibrillation in Olmsted County, Minnesota, 1980 to 2000, and Implications on the Projections for Future Prevalence
Yoko Miyasaka,Marion E. Barnes,Bernard J. Gersh,Stephen S. Cha,Kent R. Bailey,Walter P. Abhayaratna,James B. Seward,Teresa S.M. Tsang +7 more
TL;DR: The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000 and the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.
Journal ArticleDOI
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum,Carina Gross,Jan Fiedler,Thomas Fischer,Stephan Kissler,Markus Bussen,Paolo Galuppo,Steffen Just,Wolfgang Rottbauer,Stefan Frantz,Mirco Castoldi,Jürgen Soutschek,Victor Koteliansky,Andreas Rosenwald,M. Albert Basson,Jonathan D. Licht,John T. R. Pena,Sara H. Rouhanifard,Martina U. Muckenthaler,Thomas Tuschl,Gail R. Martin,Johann Bauersachs,Stefan Engelhardt,Stefan Engelhardt +23 more
TL;DR: It is shown that microRNA-21 regulates the ERK–MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function and confirms miR-21 as a disease target in heart failure and establishes the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.
Journal ArticleDOI
Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis
Eva van Rooij,Lillian B. Sutherland,Jeffrey E. Thatcher,J. Michael DiMaio,R. Haris Naseem,William S. Marshall,Joseph A. Hill,Eric N. Olson +7 more
TL;DR: It is concluded that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.