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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

Jieyun Bai, Yaosheng Lu, Andy Lo, Jichao Zhao, Henggui Zhang
2020 Annals of Translational Medicine  
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

Jieyun Bai, Yaosheng Lu, Yijie Zhu, Huijin Wang, Dechun Yin, Henggui Zhang, Diego Franco, Jichao Zhao
2021 International Journal of Molecular Sciences  
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

Yijie Zhu, Jieyun Bai, Andy Lo, Yaosheng Lu, Jichao Zhao
2021 Annals of Translational Medicine  
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

A. Chinchilla, H. Daimi, E. Lozano-Velasco, J. N. Dominguez, R. Caballero, E. Delpon, J. Tamargo, J. Cinca, L. Hove-Madsen, A. E. Aranega, D. Franco
2011 Circulation: Cardiovascular Genetics  
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

Kira Beneke, Cristina E. Molina
2021 Hearts  
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

Lan Zhang, Xi Wang, Congxin Huang
2021 Annals of Translational Medicine  
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

Emre Bektik, Douglas B. Cowan, Da-Zhi Wang
2020 International Journal of Molecular Sciences  
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

Estefanía Lozano-Velasco, Diego Franco, Amelia Aranega, Houria Daimi
2020 International Journal of Molecular Sciences  
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

Muhammad A. Balouch, Matthew J. Kolek, Dawood Darbar
2014 Global Cardiology Science & Practice  
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

Mengchen Zhou, Yuhua Liao, Xin Tu
2015 Journal of Thoracic Disease  
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

Jieyun Bai, Yijie Zhu, Andy Lo, Meng Gao, Yaosheng Lu, Jichao Zhao, Henggui Zhang
2021 International Journal of Molecular Sciences  
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

Jieyun Bai, Yaosheng Lu, Andy Lo, Jichao Zhao, Henggui Zhang
2019 Frontiers in Physiology  
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

Dawood Darbar
2016 Journal of Cardiovascular Pharmacology  
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

Dan Li, Jiali Nie, Yu Han, Li Ni
2022 Frontiers in Cardiovascular Medicine  
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

Shunsuke Tomomori, Yukiko Nakano, Hidenori Ochi, Yuko Onohara, Akinori Sairaku, Takehito Tokuyama, Chikaaki Motoda, Hiroya Matsumura, Michitaka Amioka, Naoya Hironobe, Yousaku Okubo, Shou Okamura (+5 others)
2018 Scientific Reports  
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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