Cardiac Expression of SK Channels
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB42485 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR5106580_1.fastq.gz | Fastqsanger.gz | |||
| ERR5106580_2.fastq.gz | Fastqsanger.gz | |||
| ERR5106590_1.fastq.gz | Fastqsanger.gz | |||
| ERR5106590_2.fastq.gz | Fastqsanger.gz | |||
| ERR5106600_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Note this data set has identical data files: Files GSM40994.txt and GSM40995.txt. GSE2240 contains two different experimental subsets:; 1) Comparison of atrial and ventricular gene expression (atrial tissue of patients with sinus rhythm vs. human left ventricular non-failing myocardium); The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions (Barth AS et al., Eur J Physiol, 2005). 2) Comparison of atrial gene expression in patients with permanent atrial fibrillation and sinus rhythm. Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether re-expression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression of patients with sinus rhythm as well as to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1.434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed down-regulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent up-regulation of transcripts involved in metabolic activities, suggesting an adaptive response to an increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were five times more likely to be up-regulated in atrial fibrillation (174 genes up-regulated, 35 genes down-regulated), while atrial-specific transcripts were predominantly down-regulated (56 genes up-regulated, 564 genes down-regulated). Overall, in atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be up-regulated (e.g. metabolic processes) while functional classes predominantly expressed in atrial myocardium were down-regulated in atrial fibrillation (e.g. signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium, uncovering the transcriptional response pattern in pmAF (Barth AS et al., Circ Res, 2005).
2007-10-27 | E-GEOD-2240 | biostudies-arrayexpress
Project description:Ischemic cardiomyopathy (ICM) leads to congestive heart failure and can cause sudden cardiac death due to arrhythmia. Existing molecular knowledge base of ICM is rudimentary because of lack of specific attribution to cell type and function. This study was designed to investigate cell-specific molecular remodeling of ion channels, exchangers and pumps, which are signaling molecules (SM) involved in electrical, signaling and mechanical functions of the heart. Atrial and ventricular myocytes were isolated by laser-capture microdissection from left atrium and ventricle of healthy and ICM human hearts. SM and their splice variants altered by ICM in cardiomyocytes were identified by splice microarray and validated by RT-PCR. Molecular profiling of ICM-related changes showed that SM in atrial and ventricular myocytes remodel following their unique programs. ICM affected 63 genes in ventricular myocytes and 12 genes in atrial myocytes. Only few of the identified genes were previously linked to human cardiac disfunctions. In our experiments we used 3 healthy hearts rejected from transplantation procedure and explanted ICM hearts from three male patients. Tissue samples were dissected from left ventricle and left atrial appendages. Atrial and ventricular myocytes were laser-capture microdissected from serial 7-8-µm thick cryostat sections. Individual cellular total RNA samples were analyzed on custom-built Human Ion Channel Splice Arrays slides (ExonHit) manufactured on the Ion Channel Splice Array sv1.1 platform representing 287 human SM, including 248 alternatively spliced ones in total 1655 splicing events and supplemented with capabilities to recognize connexins and ryanodine receptors.
2010-05-14 | E-GEOD-17294 | biostudies-arrayexpress
Project description:Obscurins are giant, modular, cytoskeletal proteins that regulate striated muscle structure and function. Immunoglobulin domains 58/59 (Ig58/59) of obscurin interact with diverse proteins including titin variants and phospholamban. Mutations within Ig58/59 that alter these binding interactions have been linked to the development of myopathy in humans, underscoring the pathophysiological significance of this module. We previously generated a constitutive deletion mouse model, Obscn-ΔIg58/59, that expresses obscurin lacking Ig58/59 and comprehensively characterized the effects of this deletion on cardiac morphology and function through aging. Our findings demonstrated that Obscn-ΔIg58/59 male animals develop severe arrhythmia characterized by spontaneous atrial fibrillation/junctional escape by 6-months of age, with atrial enlargement and ventricular remodeling manifesting by 12-months. Herein, we aim to mechanistically evaluate the impact of the Ig58/59 deletion in atria at the cellular level and determine the molecular basis for atrial enlargement and arrhythmia due to the physiological process of aging. Ultrastructural evaluation of sedentary aging male Obscn-ΔIg58/59 atria revealed prominent Z-disk streaming and misalignment. More importantly, Obscn-ΔIg58/59 atrial cardiomyocytes exhibited increased Ca2+ spark frequency and age-specific alterations in Ca2+ cycling kinetics and sarcoplasmic reticulum Ca2+ content that preceded those observed in Obscn-ΔIg58/59 ventricular cardiomyocytes. Proteomic and phospho-proteomic analyses revealed extensive and novel alterations in the expression and phosphorylation profile of major cytoskeletal proteins, Ca2+ regulators, and Z-disk associated protein complexes in Obscn-ΔIg58/59 atria through aging that likely underlie the observed atrial pathologies. These studies are the first to evaluate the role of obscurin in atria and to reveal chamber-specific molecular alterations due to Ig58/59 deletion. Moreover, our findings provide new molecular insights into a genetic model of spontaneous atrial fibrillation and remodeling where atrial dysfunction precedes ventricular maladaptation.
2023-04-11 | PXD028904 | Pride
Project description:GSE2240 contains two different experimental subsets: 1) Comparison of atrial and ventricular gene expression (atrial tissue of patients with sinus rhythm vs. human left ventricular non-failing myocardium) The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions (Barth AS et al., Eur J Physiol, 2005). 2) Comparison of atrial gene expression in patients with permanent atrial fibrillation and sinus rhythm. Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether re-expression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression of patients with sinus rhythm as well as to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1.434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed down-regulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent up-regulation of transcripts involved in metabolic activities, suggesting an adaptive response to an increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were five times more likely to be up-regulated in atrial fibrillation (174 genes up-regulated, 35 genes down-regulated), while atrial-specific transcripts were predominantly down-regulated (56 genes up-regulated, 564 genes down-regulated). Overall, in atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be up-regulated (e.g. metabolic processes) while functional classes predominantly expressed in atrial myocardium were down-regulated in atrial fibrillation (e.g. signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium, uncovering the transcriptional response pattern in pmAF (Barth AS et al., Circ Res, 2005). Keywords = human myocardium Keywords = atrial fibrillation Keywords = sinus rhythm Keywords = left ventricular gene expression Keywords: other
2005-05-13 | GSE2240 | GEO
Project description:Heart failure (HF) is a leading cause of mortality and is associated with cardiac remodeling. Vulnerability to atrial fibrillation (AF) has been shown to be greater in the early stages of HF, whereas ventricular tachycardia/fibrillation develop during late stages. Here, we explore changes in gene expression that underlie the differential development of fibrosis and structural alterations that predispose to atrial and ventricular arrhythmias.
2019-01-01 | GSE123823 | GEO
Project description:Ventricle arrhythmias and atrial fibrillation resulting from alternation of intracellular Ca2+ handling capacity leads to pathological cardiac hypertrophy. Junctate-1 TG mouse model is considered as a genetic model of clinical relevant atrial fibrillation. Phosphorylation is one of the most important signaling cascade for cardiac hypertrophy. To further investigate the phosphoproteome changes during abnormal Ca2+ release in junctate-1, we carried out label-free LC-MS/MS coupled with IMAC phosphopeptide enrichment.
2021-09-08 | PXD011421 | Pride
Project description:Alzheimer's disease (AD) patients exhibit neuropsychiatric symptoms that extend beyond classical cognitive deficits, suggesting involvement of subcortical areas. Here, we investigated the role of midbrain dopamine (DA) neurons in AD using the amyloid + tau-driven 3xTg-AD mouse model. We found deficits in reward-based operant learning in AD mice, suggesting possible VTA DA neuron dysregulation. Physiological assessment revealed hyperexcitability and disrupted firing in DA neurons caused by reduced activity of small-conductance calcium-activated potassium (SK) channels. RNA sequencing from contents of single patch-clamped DA neurons (Patch-seq) identified up-regulation of the SK channel modulator casein kinase 2 (CK2). Pharmacological inhibition of CK2 restored SK channel activity and normal firing patterns in 3xTg-AD mice. These findings shed light on a complex interplay between neuropsychiatric symptoms and subcortical circuits in AD, paving the way for novel treatment strategies.
2024-09-14 | GSE273040 | GEO
Project description:Atrial fibrillation (AF), the most common arrhythmia, is occasionally associated with cardiac developmental defects, but causal relationships are poorly defined. Importantly, functional compensation for developmental defects may mask increased risk of arrhythmia in adults. Here, we deleted 9 amino acids (Δ9) within a highly conserved A-band region of titin, a giant protein that serves as a molecular spring in cardiomyocytes, in both zebrafish and human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs). We find that the cardiac morphology of ttnaΔ9/Δ9 homozygous zebrafish embryos is perturbed and accompanied by reduced functional output, but ventricular function recovers within a few days of embryonic development, with most embryos reaching adulthood. Despite normal ventricular function, ttnaΔ9/Δ9 adults exhibit AF and atrial cardiomyopathy, with a striking absence of fibrosis, and these findings are recapitulated in TTNΔ9/Δ9-hiPSC-aCMs. Electrophysiological and proteomics analyses reveal atrial action potential shortening and increased expression and function of the cardiac potassium channel Kv7.1 and the slow delayed rectifier potassium current (IKs). Pharmacological suppression of IKs in both models prevents AF and improves atrial contractility. Collectively, these findings reveal how a small internal deletion in a large structural protein causes developmental abnormalities that functionally recover but increase the risk of adult cardiac disease via ion channel remodeling. The observed rescue with targeted antiarrhythmic therapy may have broader implications for the treatment of patients who harbor disease-causing rare variants in sarcomeric proteins.
2024-08-09 | PXD038300 | Pride
Project description:Previous epidemiological studies have shown that males tend to have an increased overall lifetime risk of developing atrial fibrillation (AF), whereas females tend to be more susceptible to the development of ventricular tachyarrhythmias resulting from long-QT syndrome and drug-induced Torsades de Pointes. In this study, we compared the transcript-level expression of 89 ion channel subunits, calcium handling proteins, and other transcription factors in the left atria (LA) and ventricles (LV) of human hearts of both genders.
2012-02-01 | GSE33165 | GEO
Project description:This study will report the incidence of atrial fibrillation after elective colorectal cancer resection in the over 65 age group. This will be used to validate a risk model for the development of post-operative atrial fibrillation.
Eligible patients will undergo electrocardiogram based screening for atrial fibrillation, as well as brain natriuretic peptide tests prior to surgery. They will undergo 24 hour holter monitor prior to surgery, and at 30 and 90 days following surgery.
The primary outcome will be occurrence of atrial fibrillation within 90 days of surgery. Secondary outcomes include quality of life change, use of hospital services for atrial fibrillation, and complications of atrial fibrillation. This will be used to validate the pre-existing model for prediction of atrial fibrillation.
| 2312263 | ecrin-mdr-crc