Ontology highlight
ABSTRACT:
PROVIDER: PRJNA815474 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited cardiac disease characterized by fibro-fatty replacement of the myocardium that causes heart failure and sudden cardiac death. The most aggressive subtype of ARVC is ARVC type 5 (ARVC5), caused by a p.S358L mutation in TMEM43. The function and localization of TMEM43 and the mechanism by which the p.S358L mutation causes the disease, are unknown.
2019-07-12 | GSE101301 | GEO
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of 6 ARVC specimen derived from heart transplantation candidates and compared our findings to 6 non-failing donor hearts (NF) which could not be transplanted for technical reasons. In addition, we compared our findings to 7 hearts from patients with idiopathic dilated cardiomyopathy. From each heart left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the six sample groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, unsupervised cluster analyses revealed no distinct expression pattern in LV and RV samples from ARVC-hearts. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC).
2011-11-30 | E-GEOD-29819 | biostudies-arrayexpress
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic form of heart disease often caused by mutations in desmosomal proteins. We carried out single-nucleus RNA sequencing (snRNA-seq) on 11 non-failing and 8 ARVC patient right ventricular samples and transcriptionally profiled 139,347 nuclei. We identified over 4,400 differentially expressed protein coding genes between non-failing and ARVC samples across cell types. When compared to dilated, hypertrophic and ischemic cardiomyopathy, we found that end stage ARVC is transcriptionally similar to other forms of end stage heart failure. Despite broad transcriptional similarities, we identified seven cardiomyocyte genes and six fibroblast genes that were uniquely dysregulated in ARVC and validated PLXNA4 as a gene with uniquely increased expression in cardiomyocytes in ARVC compared to other cardiomyopathies. Overexpression of PLXNA4 in hiPSC-derived ventricular cardiomyocytes induced immune response gene expression, suppressed calcium signaling, and altered cardiomyocyte electrophysiology, suggesting PLXNA4 may contribute to these pathways in ARVC.
2026-08-14 | GSE335263 | GEO
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic form of heart disease often caused by mutations in desmosomal proteins. We carried out single-nucleus RNA sequencing (snRNA-seq) on 11 non-failing and 8 ARVC patient right ventricular samples and transcriptionally profiled 139,347 nuclei. We identified over 4,400 differentially expressed protein coding genes between non-failing and ARVC samples across cell types. When compared to dilated, hypertrophic and ischemic cardiomyopathy, we found that end stage ARVC is transcriptionally similar to other forms of end stage heart failure. Despite broad transcriptional similarities, we identified seven cardiomyocyte genes and six fibroblast genes that were uniquely dysregulated in ARVC and validated PLXNA4 as a gene with uniquely increased expression in cardiomyocytes in ARVC compared to other cardiomyopathies. Overexpression of PLXNA4 in hiPSC-derived ventricular cardiomyocytes induced immune response gene expression, suppressed calcium signaling, and altered cardiomyocyte electrophysiology, suggesting PLXNA4 may contribute to these pathways in ARVC.
2026-08-14 | GSE326014 | GEO
Project description:Pathophysiology and therapeutics of arrhythmogenic right ventricular cardiomyopathy 5
| PRJNA393971 | ENA
Project description:Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy (ARVC)
| PRJNA140941 | ENA
Project description:Arrhythmogenic cardiomyopathy is an inherited entity characterized by irregular cell-cell adhesion, cardiomyocyte death, fibro-fatty replacement of ventricular myocytes, leading to malignant ventricular arrythmias, contractile dysfunction and sudden cardiac death. Pathogenic variants in genes that encode desmosome are the predominant cause of arrhythmogenic cardiomyopathy. Moreover, signalling pathways such as Wnt/ß-catenin and transforming growth factor-β have been involved in the disease progression. However, still little is known about the molecular pathophysiological mechanisms that underlie arrhythmogenic cardiomyopathy pathogenesis. We used mRNA and small RNA sequencing to analyse the transcriptome of health and arrhythmogenic cardiomyopathy autopsied human hearts. Our results showed 697 differentially expressed genes, and eight differentially expressed miRNAs. Functional enrichment revealed mitochondrial respiratory-related pathways, impaired response to oxidative stress, apoptotic signalling pathway, inflammatory response-related and extracellular matrix response pathways. Furthermore, analysis of miRNA-mRNA interactome identified eleven negatively correlated miRNA-target pairs for arrhythmogenic cardiomyopathy. Our finding revealed novel arrhythmogenic cardiomyopathy-related miRNAs with important regulatory function in disease pathogenesis highlighting their value as potential key targets for therapeutic approaches.
2025-07-24 | GSE273298 | GEO
Project description:Arrhythmogenic Right Ventricular Cardiomyopathy is a congenital heart disorder characterized by fibrofatty replacement of the myocardium. The exact molecular mechanisms underlying the disease remain to be elucidated and treatment options are limited. The sa12692 mutant line contains a splice site mutation in the plakoglobin gene, resulting in the expression of a truncated protein. This protein is highly similar to the protein expressed in Naxos disease, a recessive form of ARVC. RNA-seq was used to investigate the effect of the sa12692 mutation on gene expression in order to uncover signalling pathways involved in the pathogenesis of ARVC. Gene expression was examined in whole larvae at 5 dpf and in hearts of 1 year old adult fish. Larvae at 5 dpf were selected as this timepoint is equivalent to birth in humans. Adult hearts were selected as ARVC is a disorder of the heart and cardiac symptoms generally manifest in adulthood. Hence, the molecular effect of the mutation could be profiled at two life stages.
2021-04-30 | E-MTAB-7920 | biostudies-arrayexpress
Project description:Arrhythmogenic cardiomyopathy is an inherited entity characterized by irregular cell-cell adhesion, cardiomyocyte death, fibro-fatty replacement of ventricular myocytes, leading to malignant ventricular arrythmias, contractile dysfunction and sudden cardiac death. Pathogenic variants in genes that encode desmosome are the predominant cause of arrhythmogenic cardiomyopathy. Moreover, signalling pathways such as Wnt/ß-catenin and transforming growth factor-β have been involved in the disease progression. However, still little is known about the molecular pathophysiological mechanisms that underlie arrhythmogenic cardiomyopathy pathogenesis. We used mRNA and small RNA sequencing to analyse the transcriptome of health and arrhythmogenic cardiomyopathy autopsied human hearts. Our results showed 697 differentially expressed genes, and eight differentially expressed miRNAs. Functional enrichment revealed mitochondrial respiratory-related pathways, impaired response to oxidative stress, apoptotic signalling pathway, inflammatory response-related and extracellular matrix response pathways. Furthermore, analysis of miRNA-mRNA interactome identified eleven negatively correlated miRNA-target pairs for arrhythmogenic cardiomyopathy. Our finding revealed novel arrhythmogenic cardiomyopathy-related miRNAs with important regulatory function in disease pathogenesis highlighting their value as potential key targets for therapeutic approaches.
2024-09-30 | GSE273295 | GEO