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PITX2 upregulation increases the risk of chronic atrial fibrillation in a dose-dependent manner by modulating IKs and ICaL—insights from human atrial modelling
2020
Annals of Translational Medicine
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Functional analysis has shown that the paired-like homeodomain transcription factor 2 (PITX2) overexpression associated with atrial fibrillation (AF) leads to the slow delayed rectifier K+ current (IKs ...
Electrical remodeling (IKs and ICaL ) due to the PITX2 overexpression increases susceptibility to AF due to increased tissue vulnerability, abbreviated APD, shortened WL and altered CV, which, in combination ...
Effects of the PITX2 overexpression on CV and WL PITX2 overexpression induced electrical remodeling led to a leftward shift of the measured CVR ( Figure 4A ). ...
doi:10.21037/atm.2020.01.90
pmid:32309338
pmcid:PMC7154416
fatcat:72glxpamn5gkpg7htlpwkmz55i
Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models
2021
International Journal of Molecular Sciences
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of PITX2 in remodelling atrial structure and function to predispose to AF. ...
It is hoped that computational approaches incorporating all we know about PITX2-related structural and electrical remodelling would provide better understanding into its proarrhythmic effects leading to ...
Remodelling Linked Impaired PITX2 to AF It has been found that both overexpression and inhibition of PITX2 are related to human AF. ...
doi:10.3390/ijms22147681
fatcat:xddzhcp6jfajnmbsc47kxokeju
Mechanisms underlying pro-arrhythmic abnormalities arising from Pitx2-induced electrical remodelling: an in silico intersubject variability study
2021
Annals of Translational Medicine
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Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)-dependent gene regulation induces atrial fibrillation (AF) with different mechanisms. ...
Electrical remodelling due to Pitx2 upregulation may increase the incidence of shortened AP, whereas electrical remodelling arising from Pitx2 downregulation may favor to the genesis of triggered AP. ...
Acknowledgments We would like to thank Andy Lo and Jichao Zhao for their help in polishing the language of our paper. ...
doi:10.21037/atm-20-5660
pmid:33569408
pmcid:PMC7867875
fatcat:btpa7le22bbmflunphlqc57wwy
PITX2 Insufficiency Leads to Atrial Electrical and Structural Remodeling Linked to Arrhythmogenesis
2011
Circulation: Cardiovascular Genetics
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electric and structural remodeling linked to arrhythmogenesis. ...
Conclusions-This study thus identifies Pitx2 as an upstream transcriptional regulator of atrial electric function, the insufficiency of which results in cellular and molecular changes leading to atrial ...
level, atrial deletion of Pitx2 leads to ion channel remodeling events, which have been previously linked to familiar cases of AF, 21, 28 supporting the notion that Pitx2 acts upstream of these AF-prone ...
doi:10.1161/circgenetics.110.958116
pmid:21511879
fatcat:heexcktoifb53akdf3nnkcci3i
Molecular Basis of Atrial Fibrillation Initiation and Maintenance
2021
Hearts
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Atrial fibrillation (AF) is the most common cardiac arrhythmia, largely associated to morbidity and mortality. ...
Next, we discuss the upstream regulatory factors conducting the underlying mechanisms which drive electrical and structural AF-associated remodeling, including genetic factors (risk variants associated ...
Molecular Regulatory Networks of Proarrhythmic Mechanisms in the Atria Multiple potential mediators have been described to cause pathologic changes leading to the atrial substrate and electrical remodeling ...
doi:10.3390/hearts2010014
fatcat:h4q45obxz5bpfjm7ekawzdqtxi
A narrative review of non-coding RNAs in atrial fibrillation: potential therapeutic targets and molecular mechanisms
2021
Annals of Translational Medicine
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Atrial remodeling plays a key role in the occurrence and development of AF, and includes electrical remodeling, structural remodeling, and autonomic nerve remodeling. ...
Literatures about ncRNAs and atrial fibrillation were extensively reviewed to discuss and analyze. ...
Atrial fibrillation (AF) is common type of arrhythmia that arises due to serious disorder in the atrial electrical activity (2) . ...
doi:10.21037/atm-21-4483
pmid:34734038
pmcid:PMC8506732
fatcat:l3qnqqkymfa3hdnm5hy6qijf5e
Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System
2020
International Journal of Molecular Sciences
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Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. ...
AF can lead to decreased cardiac function, heart failure, and other complications. ...
Introduction Atrial fibrillation (AF) is the most common form of cardiac arrhythmias among heart patients [1] , which ultimately leads to heart failure and other complications, which increase morbidity ...
doi:10.3390/ijms21155424
pmid:32751460
pmcid:PMC7432754
fatcat:nz73zsry6raqbdsau4wflwf7ha
Genetics and Epigenetics of Atrial Fibrillation
2020
International Journal of Molecular Sciences
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Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. ...
heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. ...
At present, multiple microRNAs have been involved in electrical and structural remodeling directly linked to the course of atrial fibrillation ( Figure 2)
Epigenetics of Atrial Fibrillation
microRNAs ...
doi:10.3390/ijms21165717
pmid:32784971
fatcat:dsd3rkia6ncf5jdih3ed34th2y
Improved understanding of the pathophysiology of atrial fibrillation through the lens of discrete pathological pathways
2014
Global Cardiology Science & Practice
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These include pathways important for cardiac development, generation and propagation of atrial electrical impulses, and atrial remodeling and fibrosis. ...
Atrial fibrillation (AF) is a common disorder with a complex and incompletely understood pathophysiology. ...
(b) Cardiac development, electrical remodeling and atrial fibrosis are important contributors to AF development that are mediated by PITX2. ...
doi:10.5339/gcsp.2014.5
pmid:25054116
pmcid:PMC4104374
fatcat:5g2rkdijpbghrbi6vjdykz7tiu
The role of transcription factors in atrial fibrillation
2015
Journal of Thoracic Disease
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Atrial fibrillation (AF) is a complex disease that results from genetic and environmental factors and their interactions. ...
These variants exert influence on the development of cardiovascular system and normal cardiac electrical activity in different levels, and eventually contribute to the occurrence of AF. ...
So this activated angiotensin II/Rac1/STAT signaling was suggested to contribute to electrical and structural remodeling and inflammatory changes in pacing-induced AF model (62) . ...
doi:10.3978/j.issn.2072-1439.2015.01.21
pmid:25713730
pmcid:PMC4321073
fatcat:eo7ovg4m4nekdlfmt2x433srr4
In Silico Assessment of Class I Antiarrhythmic Drug Effects on Pitx2-Induced Atrial Fibrillation: Insights from Populations of Electrophysiological Models of Human Atrial Cells and Tissues
2021
International Journal of Molecular Sciences
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Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at ...
The purpose of this study was to assess the efficacy of the AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue ...
Changes in Human Atrial Electrical Activity Are Linked to Pitx2-Induced Remodelling Research studies on Pitx2-induced AF have demonstrated that Pitx2-induced remodelling contributes to atrial cellular ...
doi:10.3390/ijms22031265
pmid:33514068
pmcid:PMC7866025
fatcat:padgfjapjzhtvdesazocx2seoe
Proarrhythmia in the p.Met207Val PITX2c-Linked Familial Atrial Fibrillation-Insights From Modeling
2019
Frontiers in Physiology
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Functional analysis has shown that the p.Met207Val mutation was linked to atrial fibrillation and caused an increase in transactivation activity of PITX2c, which caused changes in mRNA synthesis related ...
In conclusion, electrical and structural remodeling arising from the PITX2c p.Met207Val mutation may increase atrial susceptibility to arrhythmia due to shortened APD, reduced CV and increased tissue vulnerability ...
The combined impact of electrical and structural remodeling on initiation and maintenance of atrial fibrillation can be characterized by atrial tissue's vulnerabilities to re-entry. ...
doi:10.3389/fphys.2019.01314
pmid:31695623
pmcid:PMC6818469
fatcat:i7kxxnt3crfdbepd7jnalinedi
The Role of Pharmacogenetics in Atrial Fibrillation Therapeutics
2016
Journal of Cardiovascular Pharmacology
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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide requiring therapy. ...
Nonetheless, recent studies have shown that common AF susceptibility risk alleles at the chromosome 4q25 locus modulated response to AADs, electrical cardioversion and ablation therapy. ...
WHY IS THERE A NEED TO 'PERSONALIZE' THERAPY FOR ATRIAL
FIBRILLATION? ...
doi:10.1097/fjc.0000000000000280
pmid:25970841
pmcid:PMC4639470
fatcat:mmevurq5yrgjtm7u2h6iagc5fa
Epigenetic Mechanism and Therapeutic Implications of Atrial Fibrillation
2022
Frontiers in Cardiovascular Medicine
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Atrial fibrillation (AF) is the most common arrhythmia attacking 1. 5–2.0% of general population worldwide. ...
Over 100 genetic loci have been discovered to be associated with AF by Genome-wide association studies (GWAS) but none has led to a therapy. ...
All authors critically revised the manuscript for important intellectual content and gave final approval for the version to be published. ...
doi:10.3389/fcvm.2021.763824
pmid:35127848
pmcid:PMC8815458
fatcat:7etpb2grkzcardqg254c4gczta
Chromosome 4q25 Variant rs6817105 Bring Sinus Node Dysfunction and Left Atrial Enlargement
2018
Scientific Reports
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Further, multiple microRNAs (miRNAs) are reported to be involved in atrial remodeling and AF pathogenesis, so we investigated relationships between rs6817105 genotype and serum concentrations of 2555 miRNAs ...
Genome-wide association studies have reported a strong association of the single nucleotide polymorphism (SNP) rs6817105 (T > C) on chromosome 4q25 with atrial fibrillation (AF), but phenotype alterations ...
The insufficiency of PITX2 was reported to result in cellular and molecular changes leading to atrial electrical and structural remodeling linked to arrhythmogenesis 6 . ...
doi:10.1038/s41598-018-32453-8
pmid:30275471
pmcid:PMC6167315
fatcat:wybr46lzozadxewchyuqnv7y4m
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