Crotonyl-proteomic analysis of right atrial tissues identified in postoperative atrial fibrillation after coronary artery bypass surgery
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ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Guowei He
PROVIDER: PXD073260 | iProX | Tue Jan 20 00:00:00 GMT 2026
REPOSITORIES: iProX
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Project description:We performed 4D-labelfree quantitative proteomics analysis of right atrial appendage tissues from 5 patients with atrial fibrillation (AF) and 5 patients with sinus rhythm (SR) after CABG. A total of 2179,559 spectrums and 48,047 peptides were detected by mass spectrometry. Further, we identified 5002 proteins, of which the number of comparable proteins was 4166. Finally, compared with SR group, 108 proteins were up-regulated and 25 proteins were down-regulated in AF group (AF/SR > 1.5, P < 0.05).
2025-08-11 | PXD059685 | Pride
Project description:Atrial fibrillation (AF), the most common cardiac rhythm disorder, is a major cause of cardiovascular morbidity and mortality. AF is characterized by the rapid and irregular activation of the atrium with diverse abnormalities, including electrical, structural, metabolic, neurohormonal, or molecular alterations.3 Although the pathophysiology of AF is complex, it has traditionally been treated with antiarrhythmic drugs that control the rhythm by altering cardiac electrical properties, principally by modulating ion channel function. However, treatments of AF with antiarrhythmic drugs have mostly failed to control the heart rhythm, because the electrical characteristics of atrial cardiomyocytes are eventually altered or remodeled during the course of AF. The aims of this study were to characterize the global changes in miRNA expression in human atrial appendages and to identify the target ion channel(s) responsible for electrical remodeling in AF. In this study, we performed a comprehensive analysis of miRNA microarrays, using a strict selection for human samples.
2017-04-25 | GSE68475 | GEO
Project description:Rationale: Circular RNAs are pervasively expressed in highly diverged eukaryotes. Circular RNAs are more stable in body fluids, however, the link between circular RNA and onset of atrial fibrillation has never been investigated. Objective: To identify plasma circular RNAs for diagnosing onset of atrial fibrillation after the cardiac surgery. Methods and Results: Plasma circular RNAs expression was investigated in participants underwent isolated off-pump coronary artery bypass grafting. First, we used microarray to screen 15 circular RNAs in 30 plasma samples for diagnosing new onset of atrial fibrillation. Quantitative polymerase chain reaction assay was then applied to evaluate the expression of selected circular RNAs. Hsa_circRNA_025016 was upregulated in patients with onset of atrial fibrillation, with a high diagnostic accuracy by area under the receiver operating characteristic curve. The satisfactory diagnostic performance of hsa_circRNA_025016 persisted in validation cohort. Kyoto Encyclopedia of Genes and Genomes biological pathway analysis indicated that hsa_circ_025016 could participate in melanogenesis, insulin secretion, and thyroid hormone signaling pathway. There was a positive correlation between hsa_circ_025016 and fast blood glucose in both cohorts. Conclusions: Hsa_circ_025016 is a novel biomarker of onset of atrial fibrillation after isolated off-pump coronary artery bypass grafting.
2017-04-07 | GSE97455 | GEO
Project description:Electrical and structural remodeling processes are contributors to the self-perpetuating nature of atrial fibrillation (AF). However, their correlation has not been clarified. In this study, human atrial tissues from the patients with rheumatic mitral valve disease in either sinus rhythm or persistent AF were analyzed using a combined transcriptomic and proteomic approach. An up-regulation in chloride intracellular channel (CLIC) 1, 4, 5 and a rise in type IV collagen were revealed. Combined with the results from immunohistochemistry and electron microscope analysis, the distribution of type IV collagen and effects of fibrosis on myocyte membrane indicated the possible interaction between CLIC and type IV collagen, confirmed by protein structure prediction and co-immunoprecipitation. These results indicate that CLICs play an important role in the development of atrial fibrillation and that CLICs and structural type IV collagen may interact on each other to promote the development of AF in rheumatic mitral valve disease.
2018-11-22 | PXD006911 | Pride
Project description:Background: Chronic atrial fibrillation (AF) is a complication associated with the dilated atria of patients with valvular heart disease and contributes to worsened pathology. Methods and Results: Using microarray technology, we examined microRNA (miR) expression profiles in right and left atrial appendage tissue from valvular heart disease (VHD) patients. Right atrial appendage from patients undergoing coronary artery bypass grafting (CABG) and left atrial (LA) appendage from healthy hearts not used for transplant were used as controls. VHD induced different changes in miR expression in LA compared with right atria (RA). Fifty-two (52) miRs were altered by VHD in LA, compared with 5 in RA tissue. There was no detectable effect of chronic AF on miR expression in LA tissue, but miR expression in RA was strongly influenced by AF, with 47 miRs showing differential expression. LA volume correlated with miR expression changes in both LA and RA, but the affected miRs were different for the two atrial groups. Conclusions: VHD and AF influence miR expression patterns in LA and RA, but these are affected differently by disease progression and by the development of AF. These findings provide new insights into the progression of VHD. RA tissue is not a useful surrogate for LA in studies of mitral valve disease. 34 arrays from either the left or right atrium from patients with Valvular Heart Disease (VHD), patients undergoing coronary artery bypass grafting (CABG), or healthy controls. Arrays in this series were generated on V2 and V3 Agilent microRNA arrays and analysed in combination.
2011-12-21 | E-GEOD-28954 | biostudies-arrayexpress
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
Project description:Background Bone morphogenetic protein 10 (BMP10) is a ligand of the TGFβ superfamily secreted mainly by atrial cardiomyocytes. Elevated BMP10 blood concentrations predict atrial fibrillation (AF), AF recurrence after ablation and AF-related cardiovascular complications like stroke. The conditions increasing BMP10 secretion and downstream effects of BMP10 in cardiomyocytes are poorly understood. We assessed BMP10 secretion dynamics and BMP10 effects in a human 3D model of atrial and ventricular engineered heart tissue (EHT). Methods Cardiomyocytes differentiated from human induced pluripotent stem cells (atrial and ventricular) were cast into a fibrin-matrix to generate EHT. Atrial EHTs were optogenetically paced (3-5 Hz) or maintained at intrinsic beating rate for 24 h up to 15 days. Release of BMP10 and other cardiac biomarkers from EHT were quantified. BMP10 plasma concentrations were compared between 1370 patients in different atrial rhythm at blood draw. Additionally, ventricular EHTs were exposed to BMP10 for 10 days. Results Atrial but not ventricular EHT released BMP10 within 48 h of culture. High rate optogenetic pacing increased atrial EHT BMP10 release by ~3-fold after a latency of at least 24 h post pacing initiation. BMP10 plasma concentrations were elevated in patients with documented AF compared to sinus rhythm and even higher in patients with current AF. BMP10 induced upregulation of TGFβ pathway transcripts, increased expression of genes related to AF and heart failure, including PITX2 and NPPB, and increased relative contraction times in ventricular EHTs. Conclusions High atrial rates elevate BMP10 expression and release, and higher plasma concentrations of BMP10 are observed in patients with active AF. BMP10 exposure induces transcriptomic changes linked to AF and heart failure in ventricular EHT. These findings support BMP10 as a biomarker and potential mediator of AF-related remodeling and tachycardiomyopathy.
2025-10-14 | GSE306533 | GEO
Project description:Atrial fibrillation (AF) is a progressive arrhythmia for which current therapy is inadequate. During AF, rapid stimulation causes atrial remodeling that promotes further AF. The cellular signals that trigger this process remain poorly understood, however, and elucidation of these factors would likely identify new therapeutic targets. We have previously shown that immortalized mouse atrial (HL-1) myocytes subjected to 24 hr of rapid stimulation in culture undergo remodeling similar to that seen in animal models of atrial tachycardia (AT) and human AF. This preparation is devoid of confounding in vivo variables that can modulate gene expression (e.g., hemodynamics). Therefore, we investigated the transcriptional profile associated with early atrial cell remodeling. RNA was harvested from HL-1 cells cultured for 24 hr in the absence and presence of rapid stimulation and subjected to microarray analysis. Data were normalized using Robust Multichip Analysis (RMA), and genes exhibiting significant differential expression were identified using the Significance Analysis of Microarrays (SAM) method. Using this approach, 919 genes were identified that were significantly altered with rapid stimulation (763 up-regulated and 156 down-regulated). For many individual transcripts, changes typical of AF/AT were observed, with marked up-regulation of genes encoding BNP and ANP precursors, heat shock proteins, and MAP kinases, while novel signaling pathways and molecules were also identified. Both stress and survival response were evident, as well as up-regulation of multiple transcription factors. Genes were also functionally classified based on cellular component, biologic process, and molecular function using the Gene Ontology database to permit direct comparison of our data with other gene sets regulated in human AF and experimental AT. For broad categories of genes grouped by functional classification, there was striking conservation between rapidly stimulated HL-1 cells and AF/AT. Results were confirmed using real-time quantitative RT-PCR on 13 genes selected by physiological relevance in AF/AT and regulation in the microarray analysis (up, down, and nonregulated). Rapidly-stimulated atrial myocytes provide a complementary experimental paradigm to explore the initial cellular signals in AT remodeling to identify novel targets in the treatment of AF. Experiment Overall Design: HL-1 cell expression profile in vitro with and without rapid electric stimulation
2008-10-26 | E-GEOD-10598 | biostudies-arrayexpress
Project description:Atrial fibrillation (AF) is the most common abnormality of heart rhythm and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies (GWAS) increased the power to detect single-nucleotide variant (SNV) associations, and we report more than 350 AF-associated genetic loci. At 139 loci we identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication. We next assayed chromatin accessibility by ATAC-seq and histone H3 Lysine 4 trimethylation in stem cell derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility of our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, we found that a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known AF risk loci will facilitate a greater understanding of the pathways underlying this heart rhythm disorder.
2024-02-08 | GSE225293 | GEO
Project description:Background Atrial fibrosis plays a critical role in the development of atrial fibrillation (AF). Exosome is a promising cell-free therapeutic approach for the treatment of AF. The purpose of this study was to explore the mechanisms underlying exosomes derived from atrial myocytes regulated atrial remodeling and ask whether their manipulation allows for therapeutic modulation of fibrosis potential abnormalities during AF. Methods We isolated exosomes from atrial myocytes and patients serum, microRNA (miRNA) sequencing analyzed the exosomal miRNAs in atrial myocytes-exosomes and patients serum-exosomes. mRNA sequencing and bioinformatics analysis corroborate the key gene as direct targets of miR-210-3p. Results The miRNAs sequencing analysis identified that miR-210-3p expression significantly increased in exosomes of tachypacing atrial myocytes and serum of AF patients. In vitro, the analysis showed that miR-210-3p inhibitor reversed tachypacing-induced proliferation and collagen synthesis in atrial fibroblasts. Accordingly, KO miR-210-3p could reduce the incidence of AF and ameliorate atrial fibrosis induced by Ang Ⅱ. The mRNA sequencing analysis and Dual-Luciferase reporter assay proved that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is the potential target gene of miR-210-3p. The functional analysis suggests that GPD1L regulated atrial fibrosis via PI3K/AKT signaling pathway. Besides, silencing GPD1L in atrial fibroblasts induced cells proliferation and these effects could be reversed by PI3K inhibitor (LY294002). Conclusion We demonstrate that atrial myocytes-derived exosomal miR-210-3p promoted the proliferation and collagen synthesis via inhibiting GPD1L in atrial fibroblasts. Preventing pathological crosstalk between atrial myocytes and fibroblasts may be as a novel target to improve atrial fibrosis in AF.
2022-08-17 | GSE210894 | GEO