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J Am Heart Assoc
2022 Apr 05;117:e023472. doi: 10.1161/JAHA.121.023472.
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MicroRNAs Regulate TASK-1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation.
Wiedmann F
,
Kraft M
,
Kallenberger S
,
Büscher A
,
Paasche A
,
Blochberger PL
,
Seeger T
,
Jávorszky N
,
Warnecke G
,
Arif R
,
Kremer J
,
Karck M
,
Frey N
,
Schmidt C
.
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Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. However, underlying molecular mechanisms are insufficiently understood. Previous studies suggested that microRNA (miRNA) dependent gene regulation plays an important role in the initiation and maintenance of AF. The 2-pore-domain potassium channel TASK-1 (tandem of P domains in a weak inward rectifying K+ channel-related acid sensitive K+ channel 1) is an atrial-specific ion channel that is upregulated in AF. Inhibition of TASK-1 current prolongs the atrial action potential duration to similar levels as in patients with sinus rhythm. Here, we hypothesize that miRNAs might be responsible for the regulation of KCNK3 that encodes for TASK-1. Methods and Results We selected miRNAs potentially regulating KCNK3 and studied their expression in atrial tissue samples obtained from patients with sinus rhythm, paroxysmal AF, or permanent/chronic AF. MiRNAs differentially expressed in AF were further investigated for their ability to regulate KCNK3 mRNA and TASK-1 protein expression in human induced pluripotent stem cells, transfected with miRNA mimics or inhibitors. Thereby, we observed that miR-34a increases TASK-1 expression and current and further decreases the resting membrane potential of Xenopus laevis oocytes, heterologously expressing hTASK-1. Finally, we investigated associations between miRNA expression in atrial tissues and clinical parameters of our patient cohort. A cluster containing AF stage, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, atrial COL1A2 (collagen alpha-2(I) chain), and TASK-1 protein level was associated with increased expression of miR-25, miR-21, miR-34a, miR-23a, miR-124, miR-1, and miR-29b as well as decreased expression of miR-9 and miR-485. Conclusions These results suggest an important pathophysiological involvement of miRNAs in the regulation of atrial expression of the TASK-1 potassium channel in patients with atrial cardiomyopathy.
Adam,
Role of miR-21 in the pathogenesis of atrial fibrosis.
2012, Pubmed
Adam,
Role of miR-21 in the pathogenesis of atrial fibrosis.
2012,
Pubmed
Agarwal,
Predicting effective microRNA target sites in mammalian mRNAs.
2015,
Pubmed
Bartel,
MicroRNAs: genomics, biogenesis, mechanism, and function.
2004,
Pubmed
Betel,
The microRNA.org resource: targets and expression.
2008,
Pubmed
Boon,
MicroRNA-34a regulates cardiac ageing and function.
2013,
Pubmed
Burridge,
Chemically defined generation of human cardiomyocytes.
2014,
Pubmed
Cardin,
Role for MicroRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure.
2012,
Pubmed
Chugh,
Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study.
2014,
Pubmed
Corcoran,
miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression.
2014,
Pubmed
Cosín-Tomás,
Plasma miR-34a-5p and miR-545-3p as Early Biomarkers of Alzheimer's Disease: Potential and Limitations.
2017,
Pubmed
Dawson,
MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation.
2013,
Pubmed
Decher,
Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a disturbed QRS complex.
2011,
Pubmed
Dobrev,
The G protein-gated potassium current I(K,ACh) is constitutively active in patients with chronic atrial fibrillation.
2005,
Pubmed
Donner,
Functional role of TASK-1 in the heart: studies in TASK-1-deficient mice show prolonged cardiac repolarization and reduced heart rate variability.
2011,
Pubmed
Duisters,
miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling.
2009,
Pubmed
Farberov,
MicroRNA-mediated regulation of p21 and TASK1 cellular restriction factors enhances HIV-1 infection.
2015,
Pubmed
Feldman,
Analysis of Circulating miR-1, miR-23a, and miR-26a in Atrial Fibrillation Patients Undergoing Coronary Bypass Artery Grafting Surgery.
2017,
Pubmed
Feliciangeli,
The family of K2P channels: salient structural and functional properties.
2015,
Pubmed
Filipowicz,
Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
2008,
Pubmed
Frustaci,
Histological substrate of atrial biopsies in patients with lone atrial fibrillation.
1997,
Pubmed
Girmatsion,
Changes in microRNA-1 expression and IK1 up-regulation in human atrial fibrillation.
2009,
Pubmed
Han,
MiR-34a, miR-21 and miR-23a as potential biomarkers for coronary artery disease: a pilot microarray study and confirmation in a 32 patient cohort.
2015,
Pubmed
Huang,
Identification of serum miR-34a as a potential biomarker in acute myeloid leukemia.
2018,
Pubmed
Inui,
MicroRNA control of signal transduction.
2010,
Pubmed
Jin,
Effect of miR-9 on myocardial fibrosis in rats via TGF-β1/Smads signaling pathway.
2019,
Pubmed
Kassem,
Circulating miR-34a and miR-125b as Promising non Invasive Biomarkers in Egyptian Locally Advanced Breast Cancer Patients.
2019,
Pubmed
Krishna,
Structure and function of negative feedback loops at the interface of genetic and metabolic networks.
2006,
Pubmed
Li,
Expression of miR-133 and miR-30 in chronic atrial fibrillation in canines.
2012,
Pubmed
Lian,
Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions.
2013,
Pubmed
Limberg,
TASK-1 channels may modulate action potential duration of human atrial cardiomyocytes.
2011,
Pubmed
,
Xenbase
Lin,
miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy.
2009,
Pubmed
Liu,
Catheter ablation restores decreased plasma miR-409-3p and miR-432 in atrial fibrillation patients.
2016,
Pubmed
Lu,
Expression profile analysis of circulating microRNAs and their effects on ion channels in Chinese atrial fibrillation patients.
2015,
Pubmed
Luo,
MicroRNAs and atrial fibrillation: mechanisms and translational potential.
2015,
Pubmed
Luo,
MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation.
2013,
Pubmed
Martinez,
A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity.
2008,
Pubmed
McManus,
Relations between circulating microRNAs and atrial fibrillation: data from the Framingham Offspring Study.
2014,
Pubmed
Mitrophanov,
Positive feedback in cellular control systems.
2008,
Pubmed
Nunez,
Positively correlated miRNA-mRNA regulatory networks in mouse frontal cortex during early stages of alcohol dependence.
2013,
Pubmed
Nunez-Iglesias,
Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation.
2010,
Pubmed
Olschewski,
Impact of TASK-1 in human pulmonary artery smooth muscle cells.
2006,
Pubmed
Percie du Sert,
Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0.
2020,
Pubmed
Poudel,
Atrial fibrillation: recent advances in understanding the role of microRNAs in atrial remodeling with an electrophysiological overview.
2015,
Pubmed
Reilly,
Up-regulation of miR-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase.
2016,
Pubmed
Schmidt,
Inverse remodelling of K2P3.1 K+ channel expression and action potential duration in left ventricular dysfunction and atrial fibrillation: implications for patient-specific antiarrhythmic drug therapy.
2017,
Pubmed
Schmidt,
Upregulation of K(2P)3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation.
2015,
Pubmed
Schmidt,
Prospective multicentric validation of a novel prediction model for paroxysmal atrial fibrillation.
2021,
Pubmed
Schneider,
NIH Image to ImageJ: 25 years of image analysis.
2012,
Pubmed
Sciandra,
Circulating miR34a levels as a potential biomarker in the follow-up of Ewing sarcoma.
2020,
Pubmed
Skarsfeldt,
pH-dependent inhibition of K₂P3.1 prolongs atrial refractoriness in whole hearts.
2016,
Pubmed
Slagsvold,
Mitochondrial respiration and microRNA expression in right and left atrium of patients with atrial fibrillation.
2014,
Pubmed
Søkilde,
Passenger strand loading in overexpression experiments using microRNA mimics.
2015,
Pubmed
Sun,
Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma.
2012,
Pubmed
Thomson,
On measuring miRNAs after transient transfection of mimics or antisense inhibitors.
2013,
Pubmed
Thum,
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts.
2008,
Pubmed
Vasudevan,
Switching from repression to activation: microRNAs can up-regulate translation.
2007,
Pubmed
Voigt,
Cellular and molecular mechanisms of atrial arrhythmogenesis in patients with paroxysmal atrial fibrillation.
2014,
Pubmed
Voigt,
Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation.
2012,
Pubmed
Wang,
miR-9 and NFATc3 regulate myocardin in cardiac hypertrophy.
2010,
Pubmed
Wang,
miRNA-34a promotes proliferation of human pulmonary artery smooth muscle cells by targeting PDGFRA.
2016,
Pubmed
Wiedmann,
N-glycosylation-dependent regulation of hK2P17.1 currents.
2019,
Pubmed
,
Xenbase
Xu,
Atrial extracellular matrix remodeling and the maintenance of atrial fibrillation.
2004,
Pubmed
Zhu,
MicroRNA‑34a mediates atrial fibrillation through regulation of Ankyrin‑B expression.
2018,
Pubmed
