Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profile in the atrial fibrillation patient hearts across seven heart regions

ABSTRACT: Atrial fibrillation (AF) is the most frequent persistent arrhythmia, and many genes have been reported as a causal gene candidate for AF. However, most transcriptome analyses of AF have limited to the atrial samples and have not evaluated by multiple cardiac regions. In this study, we analyzed the expression levels of protein-coding and long noncoding RNAs (lncRNAs) in six different cardiac regions by RNA-seq. Surprisingly, the most changed region in gene expression by the presence of AF was the pulmonary vein (PV), not the atria. Upon analysis of these significant genes, the ion channel-related gene set was significantly enriched. In addition, cancer-related lncRNAs was up-regulated in PV in AF. A Co-expression network analysis could detect the functional gene clusters. In particular, the functional coupling between the lncRNA FOXCUT and transcription factor FOXC1 are known to be involved in process of the epithelial-mesenchymal transition in cancer tissues. Thus, they may also play an aggravating role in the pathogenesis of AF. In the least, this study suggests that (1) RNA alteration is most intense in PVs and (2) post-acquired gene regulation, such as the FOXCUT-FOXC1 axis, may contribute to the progression of AF.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226283 | GEO | 2023/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profile in the atrial fibrillation patient right atrial appendages

Project description:Atrial fibrillation (AF) is the most frequent persistent arrhythmia, and many genes have been reported as a causal gene candidate for AF. However, most transcriptome analyses of AF have limited to the atrial samples and have not evaluated by multiple cardiac regions. In this study, we analyzed the expression levels of protein-coding and long noncoding RNAs (lncRNAs) in six different cardiac regions by RNA-seq. Surprisingly, the most changed region in gene expression by the presence of AF was the pulmonary vein (PV), not the atria. Upon analysis of these significant genes, the ion channel-related gene set was significantly enriched. In addition, cancer-related lncRNAs was up-regulated in PV in AF. A Co-expression network analysis could detect the functional gene clusters. In particular, the functional coupling between the lncRNA FOXCUT and transcription factor FOXC1 are known to be involved in process of the epithelial-mesenchymal transition in cancer tissues. Thus, they may also play an aggravating role in the pathogenesis of AF. In the least, this study suggests that (1) RNA alteration is most intense in PVs and (2) post-acquired gene regulation, such as the FOXCUT-FOXC1 axis, may contribute to the progression of AF.

2023-04-30 | GSE226282 | GEO

Decoding the PITX2 controlled genetic network in atrial fibrillation

Project description:Atrial fibrillation (AF), the most common sustained cardiac arrhythmia and a major risk factor for stroke, often arises through ectopic electrical impulses derived from the pulmonary veins (PV). Sequence variants in enhancers controlling expression of the transcription factor PITX2, which is expressed in the cardiomyocytes (CMs) of the PV and left atrium (LA), have been implicated in AF predisposition. Single nuclei multiomic profiling of RNA and analysis of chromatin accessibility combined with spectral clustering uncovered distinct PV- and LA-enriched CM cell states. Pitx2 mutant PV and LA CMs exhibited gene expression changes consistent with cardiac dysfunction through cell-type-distinct, PITX2-directed, cis-regulatory grammars controlling target gene expression. The perturbed network targets in each CM were enriched in distinct human AF-predisposition genes, suggesting combinatorial risk for AF-genesis. Our data further reveals that PV and LA Pitx2 mutant CMs signal to endothelial and endocardial cells through BMP10 signaling with pathogenic potential. This work provides a multiomic framework for interrogating the basis of AF-predisposition in the PV of humans.

2022-04-28 | GSE183310 | GEO

Heart proteomics of pathological atrial enlargement associated with atrial fibrillation

Project description:Atrial fibrillation (AF) remains challenging to prevent and treat. It is associated with increased rates of heart failure, stroke and neurological decline. A key feature of AF is atrial enlargement. However, not all atrial enlargement progresses to pathology and AF. In the current study, we characterized mouse atria from a 1) pathological model (cardiac-specific transgenic (Tg) that develops dilated cardiomyopathy [DCM] and AF due to reduced protective signalling [PI3K]; DCM-dnPI3K), and a 2) physiological model (cardiac-specific Tg with an enlarged heart due to increased insulin-like growth factor 1 receptor; IGF1R). Atrial enlargement in the DCM-dnPI3K Tg, but not IGF1R Tg, was associated with atrial dysfunction, fibrosis and a heart failure gene expression pattern. Proteomics analysis identified proteins and pathways that were differentially regulated in pathological and physiological atrial enlargement, and provides a resource to study potential drug targets for AF.

2023-12-07 | MSV000093605 | MassIVE

Loss of the Atrial Fibrillation-related gene, Zfhx3, Results in Atrial Dilation and Arrhythmias by Disruption of Genes Essential for Cardiovascular Homeostasis

Project description:Background: ZFHX3, a gene that encodes a large transcription factor, is the second-most significantly associated locus with AF, but its function in the heart is unknown. This study aims to identify causative genetic variation related to AF at the ZFHX3 locus and examine the impact of Zfhx3 loss on cardiac function in mice. Methods: CRISPR-Cas9 genome editing, chromatin immunoprecipitation, and luciferase assays in pluripotent stem cell-derived cardiomyocytes were used to identify causative genetic variation related to AF at the ZFHX3 locus. Cardiac function was assessed by echocardiography, MRI, electrophysiology studies, calcium imaging, and RNA sequencing in mice with heterozygous and homozygous cardiomyocyte-restricted Zfhx3 deletion (Zfhx3 Het and KO, respectively). Human cardiac single-nucleus ATAC-sequencing data was analyzed to determine which genes in atrial cardiomyocytes are directly regulated by ZFHX3. Results: We found SNP rs12931021 modulates an enhancer regulating ZFHX3 expression, and the AF risk allele is associated with decreased ZFHX3 transcription. We observed a gene-dose response in AF susceptibility withZfhx3KO mice having higher incidence, frequency, and burden of AF thanZfhx3Het and WT mice, with alterations in conduction velocity, atrial action potential duration, calcium handling and the development of atrial enlargement and thrombus, and dilated cardiomyopathy. Zfhx3 loss results in atrial-specific differential effects on genes and signaling pathways involved in cardiac pathophysiology and AF. Conclusions: Our findings implicate ZFHX3 as the causative gene at the 16q22 locus for AF, and cardiac abnormalities caused by loss of cardiac Zfhx3 are due to atrial-specific dysregulation of pathways involved in AF-susceptibility. Together, these data reveal a novel and important role for Zfhx3 in the control of cardiac genes and signaling pathways essential for normal atrial function.

2023-06-30 | GSE229525 | GEO

Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for atrial fibrillation

Project description:We identified 177 lncRNAs and 153 mRNAs that were differentially expressed (â?¥ 2-fold change), indicating that many lncRNAs are significantly upregulated or downregulated in AF. Among these, NONHSAT040387 and NONHSAT098586 were the most up-regulated and downregulated lncRNAs, and were selected for validation via quantitative PCR. GO analysis and KEGG pathway were applied to exploring potential lncRNAs function, identifying several pathways were alerted in atrial fibrillation pathogenesis. we investigated the expression patterns of lncRNAs and mRNAs from atrial fibrillation with Agilent Human lncRNA array V4.0 (4 Ã? 180 K), which include 78,243 human lncRNAs and 30,215 coding transcripts.

2016-07-03 | E-GEOD-64904 | biostudies-arrayexpress

Profiling of long non-coding RNAs associated with atrial fibrillation in patients with rheumatic heart valvular disease

Project description:To investigate the expression profiles of long non-coding RNAs (lncRNAs) in atrial fibrillation (AF), atrial tissues from 5 AF patients and 5 non-AF patients that were collected for lncRNA expression microarray analyses to explore the role of lncRNA in the pathogenesis of AF.rhythm (SR) patients with rheumatic heart valvular disease,we have employed

2018-01-03 | GSE108660 | GEO

Integrated Analysis of Dysregulated lncRNA and mRNA Expression profiles of myocardial sleevesof pulmonary veins in atrial fibrillation

Project description:Atrial fibrillation (AF) is currently the most prevalent arrhythmia worldwide.Recent clinical data implicate the additional contribution of non-coding RNAs in the pathogenesis of AFï¼which include microRNAs(miRNAs), endogenous small interfering RNAs, PIWIinteracting RNAs, and lncRNA. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with AF has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNA and mRNA expression profiles in myocardial sleevesof pulmonary veins between the patients who develop AF and the patients who were in normal sinus rhythm, which was performed using a second generation lncRNA microarrayï¼focusing specifically on the identification and characterization of lncRNAs and mRNA potentially involving in maintaining atrial fibrillation. We conducted an integrated analysis of myocardial sleeves of pulmonary veinsï¼PVsï¼from 12 patients (6 non-AF and 6AF) in our center, of which hypertension, diabetes, smoking and alcohol abuse were excluded, using a second generation lncRNA microarray

2016-01-16 | E-GEOD-76899 | biostudies-arrayexpress

Rac1-Induced Connective Tissue Growth Factor regulates Connexin 43 and N-Cadherin Expression in Atrial Fibrillation

Project description:Objectives: We studied the signal transduction of atrial structural remodelling that contributes to the pathogenesis of atrial fibrillation (AF). Backround: Fibrosis is a hallmark of arrhythmogenic structural remodelling but the underlying molecular mechanisms are incompletely understood. Methods: We performed transcriptional profiling of left atrial myocardium (LA) from patients with AF and sinus rhythm (SR) and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) who develop AF at old age to characterize mediators of the signal transduction of atrial remodeling. Results: LA from patients with AF showed a marked upregulation of connective tissue growth factor (CTGF) expression compared SR patients. This was associated with increased fibrosis, NADPH-oxidase-, Rac1- and RhoA activity, upregulation of N-cadherin and connexin 43 (Cx43) expression and increased angiotensin II tissue concentration. In neonatal rat cardiac myocytes and -fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II induced upregulation of CTGF, Cx43 and N-cadherin expression. Transfection with small-inhibiting CTGF RNA blocked Cx43 and N-cadherin expression. RacET mice showed upregulation of CTGF, Cx43 and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo. Conclusion: The data identify CTGF as an important mediator of atrial structural remodelling during AF. Angiotensin II activates CTGF via activation of Rac1 and NADPH oxidase, leading to upregulation of Cx43, N-cadherin and interstitial fibrosis and therefore contributing to the signal transduction of atrial structural remodelling. Array design study consists of 5 Atrial Fibrillation patients and matched 5 samples of patients in sinus rhythm (controls).

2010-02-21 | E-GEOD-14975 | biostudies-arrayexpress

Transcriptome and Proteome Mapping in the Sheep Atria Reveal Molecular Features of Atrial Fibrillation Progression

Project description:Atrial fibrillation (AF) is often a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for AF, as well as the fundamental mechanisms governing the transition from paroxysmal to persistent and permanent forms. We aimed to create a molecular map of AF and find the distinct genetic programs underlying cell type-specific atrial remodeling and AF progression. We used a sheep model of long-standing, tachypacing-induced AF, sampled right and left atrial tissue and isolated cardiomyocytes from control, intermediate (transition) and late time points during AF progression, and performed transcriptomic and proteome profiling. We have merged all these layers of information into a meaningful 3-component space in which we explored the genes and proteins detected and their common patterns of expression. Our data-driven analysis points at extracellular matrix remodeling, inflammation, ion channel, myofibril structure, mitochondrial complexes and chromatin remodeling as hallmarks of AF progression. Most important, we prove that these changes occur at early transitional stages of the disease, but not at later stages, and that the left atrium undergoes significantly more profound changes than the right atrium in its expression program. The pattern of dynamic changes in gene and protein expression correspond closely with the electrical and structural remodeling demonstrated previously in the sheep and in humans. The results provide novel insight into the dynamics of gene and protein expression changes that underlie AF-induced atrial remodeling and that make the arrhythmia become more stable and long lasting.

2021-01-08 | PXD015637 | Pride

Large-scale Single-nuclei Profiling Identifies Role for ATRNL1 in Atrial Fibrillation [snRNA-seq]

Project description:Atrial fibrillation (AF) is the most common sustained arrhythmia in humans, yet the molecular basis of AF remains incompletely understood. To determine the cell type-specific transcriptional changes underlying AF, we performed single-nucleus RNA-seq (snRNA-seq) on age- and sex-matched left atrial (LA) samples from 18 patients with AF and 16 controls without AF. From more than 175,000 nuclei we identified 15 cell types but found that only cardiomyocytes (CMs) and macrophages (MΦs) had a significant number of differentially expressed genes in patients with AF. Attractin Like 1 (ATRNL1) was strongly overexpressed in CMs among patients with AF and localized to the intercalated discs. Further, in both knockdown and overexpression experiments in atrial human embryonic stem cell-derived CMs (hESC-aCMs) we identified a potent role for ATRNL1 in cell stress response, cardiac conduction, cell junction organization and in modulation of the cardiac action potential. Finally, we prioritized genes at the known genetic loci for AF and identified an unexpected expression for a leading AF candidate gene, KCNN3. In sum, we have identified a role for ATRNL1 and other differentially regulated genes that may serve as potential therapeutic targets for this common arrhythmia.

2024-09-24 | GSE255612 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data