MicroRNAs Regulate TASK‐1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation

Wiedmann, Felix; Kraft, Manuel; Kallenberger, Stefan M.; Büscher, Antonius; Paasche, A; Blochberger, P; Seeger, Timon; Jávorszky, Natasa; Warnecke, G.; Arif, Rawa; Kremer, Jamila; Kretzler, Matthias; Frey, Norbert; Schmidt, Constanze

doi:10.1161/jaha.121.023472

Cited by 19 publications

(14 citation statements)

References 63 publications

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“…Other miRNAs differentially expressed in both human induced pluripotent stem cells (hiPSCs) and atrial tissue samples from AF patients have been recently evaluated [ 98 ]. In particular, miR-34a regulates atrial TASK-1 (tandem of P-domains in a weak inward rectifying K + channel- related acid sensitive K + channel 1) potassium channels and has been proposed as an important contributor to the initiation and maintenance of AF, linked to myocardial dilation.…”

Section: Mirnas Involved In Afib Ed and Af And Their Putative Role As...mentioning

confidence: 99%

microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation

Desantis

Potenza

Sgarra

et al. 2023

IJMS

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The pathophysiology of atrial fibrillation (AF) may involve atrial fibrosis/remodeling and dysfunctional endothelial activities. Despite the currently available treatment approaches, the progression of AF, its recurrence rate, and the high mortality risk of related complications underlay the need for more advanced prognostic and therapeutic strategies. There is increasing attention on the molecular mechanisms controlling AF onset and progression points to the complex cell to cell interplay that triggers fibroblasts, immune cells and myofibroblasts, enhancing atrial fibrosis. In this scenario, endothelial cell dysfunction (ED) might play an unexpected but significant role. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level. In the cardiovascular compartment, both free circulating and exosomal miRNAs entail the control of plaque formation, lipid metabolism, inflammation and angiogenesis, cardiomyocyte growth and contractility, and even the maintenance of cardiac rhythm. Abnormal miRNAs levels may indicate the activation state of circulating cells, and thus represent a specific read-out of cardiac tissue changes. Although several unresolved questions still limit their clinical use, the ease of accessibility in biofluids and their prognostic and diagnostic properties make them novel and attractive biomarker candidates in AF. This article summarizes the most recent features of AF associated with miRNAs and relates them to potentially underlying mechanisms.

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Section: Mirnas Involved In Afib Ed and Af And Their Putative Role As...mentioning

confidence: 99%

microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation

Desantis

Potenza

Sgarra

et al. 2023

IJMS

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show abstract

“…Furthermore, the breathing stimulant compound doxapram inhibits human TASK-1 and TASK-3 channels with equal potency and can be used in a novel pharmacological strategy for cardioversion of acute episodes of paroxysmal AF as well as the rhythm control of persistent AF [ 47 ]. Several other experiments have also shown that the targeted inhibition of TASK-1 channels can effectively treat AF, confirming that it is an antiarrhythmic target in general [ 48 , 49 , 50 , 51 ]. In addition to the regulation of vascular tone in pulmonary arteries, TASK-1 channels also play an important vasomotor role in systemic arteries under specific conditions or at certain stages of ontogenesis.…”

Section: The Biological Roles Of Task Channelsmentioning

confidence: 83%

Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets

Fan

et al. 2022

Molecules

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TWIK-related acid-sensitive K+ (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K2P) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sensitive to changes in extracellular pH and are active during all membrane potential periods. They are similar to other K2P channels in that they can create and use background-leaked potassium currents to stabilize resting membrane conductance and repolarize the action potential of excitable cells. TASK channels are expressed in both the nervous system and peripheral tissues, including excitable and non-excitable cells, and are widely engaged in pathophysiological phenomena, such as respiratory stimulation, pulmonary hypertension, arrhythmia, aldosterone secretion, cancers, anesthesia, neurological disorders, glucose homeostasis, and visual sensitivity. Therefore, they are important targets for innovative drug development. In this review, we emphasized the recent advances in our understanding of the biophysical properties, gating profiles, and biological roles of TASK channels. Given the different localization ranges and biologically relevant functions of TASK-1 and TASK-3 channels, the development of compounds that selectively target TASK-1 and TASK-3 channels is also summarized based on data reported in the literature.

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“…Belevych 2016) revealed experimentally that miRNA-1 drives arrhythmogenesis by altering ion channels and proteins associated with the heart's electrical activity in cardiac diseases [40][41][42][43]. Also, Wiedmann et al [44] aimed to study differential expression of selected miRNA in atrial tissue samples obtained from patients with sinus rhythm, paroxysmal AF, or permanent/chronic AF, and they found that miR-25, miR-21, miR-34a, miR-23a, miR-124, miR-1, and miR-29b upregulation as well as miR-9 and miR-485 downregulation were associated with TASK-1 potassium channel in patients with atrial cardiomyopathy. The above results conclude the disturbance of cardiac ion channel proteins resulting from dysregulated miRNAs may be one of cardiac diseases pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

miR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients

et al. 2022

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Background Childhood dilated cardiomyopathy (CDCM) is the most common cardiomyopathy in children and it is risk factor to heart failure and sudden death. Most of the different etiologic factors which have been postulated to DCM are idiopathic, and its pathogenesis remains uncertain. So it was worth investigating the potential DCM pathogenicity models to establish early noninvasive diagnosis parameters especially in CDCM patients. Beside that miRNAs in the circulatory blood are genetically considered the best option for noninvasive diagnosis; also, implementation of miRNAs as early diagnostic markers for children with DCM is urgent because those children have high risk to sudden heart death. We aimed to identify discriminator diagnostic circulatory miRNA expression levels in CDCM patients. Results The expression levels of miR-454-3p and miR-194-5p were found significant upregulated (p value = 0.001 and 0.018; CI 95%, respectively), while miR-875-3p was found significant downregulated (p value = 0.040; CI 95%). A receiver operating characteristic (ROC) curve analysis showed significant AUC = 1.000 and 0.798 for miR-454-3p and miR-194-5p, respectively, and the optimal discriminated diagnostic cut-points were computed by index of union (IU) method. Enrichment analysis for the potential targeted mature mRNAs by miR-454-3p and miR-194-5p pointed that Ca, Na and K ions homeostasis in cardiac sarcolemma consider potential CDCM pathogenicity model. Conclusions miR-454-3p and miR-194-5p are highly influencing noninvasive biomarkers for CDCM, and further circulatory miRNAs-implicated studies are highly recommended.

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MicroRNAs Regulate TASK‐1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation

Cited by 19 publications

References 63 publications

microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation

microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation

Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets

miR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients

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