Whole genome microarray gene expression profiling of right ventricular heart specimens from pediatric patients with Tetralogy of Fallot (TOF)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE241024 | GEO | 2023/09/18
REPOSITORIES: GEO
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Project description:The most common congenital heart disease (CHD) is the ventricular septal defect (VSD), which is also a subfeature of Tetralogy of Fallot (TOF) representing the most common form of cyanotic CHD. The underlying causes for the majority of CHDs are still unclear and most probably consist of combinations of genetic, epigenetic and environmental factors. DNA methylation is the most widely studied epigenetic modification and several cardiac regulators have already been shown to be differentially methylated in CHD patients. Here, we present the first analysis of genome-wide DNA methylation data obtained from cardiac biopsies of TOF and VSD patients. We applied affinity-based enrichment of methylated DNA sequences with methyl-CpG-binding domain proteins followed by next-generation sequencing (MBD-Seq). MBD-seq on cardiac biopsies of patients with Tetralogy of Fallot and ventricular septal defect
2016-08-08 | E-GEOD-62629 | biostudies-arrayexpress
Project description:The most common congenital heart disease (CHD) is the ventricular septal defect (VSD), which is also a subfeature of Tetralogy of Fallot (TOF) representing the most common form of cyanotic CHD. The underlying causes for the majority of CHDs are still unclear and most probably consist of combinations of genetic, epigenetic and environmental factors. DNA methylation is the most widely studied epigenetic modification and several cardiac regulators have already been shown to be differentially methylated in CHD patients. Here, we present the first analysis of genome-wide DNA methylation data obtained from cardiac biopsies of TOF and VSD patients. We applied affinity-based enrichment of methylated DNA sequences with methyl-CpG-binding domain proteins followed by next-generation sequencing (MBD-Seq).
2016-08-08 | GSE62629 | GEO
Project description:<p><strong>INTRODUCTION: </strong>Transposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress.</p><p><strong>OBJECTIVE: </strong>We aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery.</p><p><strong>METHODS:</strong> We studied 14 TGA newborns with intact ventricular septum undergoing arterial switch operation with the use of CPB. Urine samples were collected preoperatively and at the end of the surgery and were analyzed using an untargeted metabolomics approach based on UHPLC-high resolution mass spectrometry.</p><p><strong>RESULTS:</strong> Since post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. This library was applied to our samples and 1255 drugs and drug metabolites were excluded from the analysis. Afterward, we detected over 39,000 unique compounds and 371 putatively annotated metabolites were different between pre and post-surgery samples. Among these metabolites, 13 were correctly annotated or identified. Metabolites linked to kynurenine pathway of tryptophan degradation displayed the highest fold change.</p><p><strong>CONCLUSIONS:</strong> This is the first report on metabolic response to cardiac surgery in TGA newborns. We developed an experimental design that allowed the identification of perturbed metabolic pathways and potential biomarkers of brain damage, limiting drugs interference in the analysis.</p>
2020-04-15 | MTBLS946 | MetaboLights
Project description:This is the first report characterizing noncoding RNA expression in a congenital heart defect. The striking shift in expression of noncoding RNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing and translation of developmentally important genes and possibly contributing to the cardiac defect. The importance of noncoding RNAs (ncRNA), especially microRNAs, for maintaining stability in the developing vertebrate heart has recently become apparent. However, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants. We found 61 microRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a remarkable resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of microRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 microRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and two spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of the critical cardiac developmental genes. Taken together, these observations suggest a link between snoRNA level in the myocardium, spliceosomal function and heart development. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants
2012-07-11 | E-GEOD-35490 | biostudies-arrayexpress
Project description:Tetralogy of Fallot (ToF) and Atrial Septal Defects (ASD) are the most common types of congenital heart disease and a major cause of childhood morbidity and mortality. Cardiopulmonary bypass (CPB) is used during corrective cardiac surgery to support circulation and heart stabilization. However, this technique triggers systemic inflammatory and stress response and consequent increased risk of postoperative complications. The aim of this study was to define the molecular bases of ToF and ASD pathogenesis and response to CPB and identify new specific biomarkers. We conducted comparative transcriptome analysis of right atrial biopsies from 10 ToF and 10 ASD patients before (Pre-CPB) and after (Post-CPB) surgery. Pre-CPB samples showed significant differential expression of 72 genes (DEGs), 28 of which were overexpressed in ToF and 44 in ASD. According to Gene Ontology annotation, the mostly enriched biological processes were represented by matrix organization and cell adhesion in ToF and by muscle development and contractility in ASD specimens. GSEA highlighted the specific enrichment of known hypoxia gene sets in ToF samples, pointing to a role for hypoxia in disease pathogenesis. The post-CPB myocardium exhibited significant alterations in the expression profile of genes related to transcription regulation, growth/apoptosis, inflammation, cell adhesion/matrix organization, and oxidative stress. Among DEGs, only 70 were common to the two disease groups, whereas 110 and 24 were unique in ToF and ASD, respectively. Interestingly, gene expression changes in ASD samples followed a consensus hypoxia profile. These data define ToF- and ASD-specific myocardial transcriptional signatures and demonstrate differential gene reprogramming in response to CPB in the two pathologies, with potential prognostic and therapeutic implications.
2020-01-21 | GSE132176 | GEO
Project description:The protein BBLN with largely unknown function was identified in human right ventricular heart specimens from patients undergoing repair surgery for Tetralogy of Fallot (TOF). Proteins from heart specimens were solubilized and subjected to immuno-affinity enrichment with anti-CAMK2D-specific antibodies. Co-enriched proteins were separated by SDS-PAGE, and the protein band in the range of 8-14 kDa was cut and subjected to identification by nano-LC-ESI-MS/MS.
2023-09-18 | PXD044695 | Pride
Project description:Small RNAs, especially the microRNAs, have been revealed to play great roles in heart development and congenital heart defects. Several studies have shown dysregulated miRNAs in ventricular tissues of Tetralogy of Fallot (TOF) patients. In the present study, we conducted high throughput sequencing to obtain the global profiling of small RNA transcriptome in heart right ventricular samples from 10 age -matched TOF patients. These samples showed dominant composition of miRNA and mitochondrial associated RNAs. By sRNA cluster identification and differential gene expression analysis, significant sexual difference was discovered for sRNA expression in TOF patients. miR-1/miR-133, the first identified miRNA cluster essential for cardiac development, account for the most variance of sRNA expression between sexes. Our results suggested divergent molecular basis between female and male TOF patients.
2018-12-21 | GSE113511 | GEO
Project description:Congenital heart disease is a congenital defect with a very high morbidity and mortality rate, of which Cyanotic Congenital Heart Disease (CCHD) is the most severe type.Due to the special anatomical changes of CCHD, the blood of the right ventricle cannot enter the pulmonary capillaries for full oxygenation, directly flows into the left ventricle and further flows into the systemic circulation, resulting in long-term hypoxia.Therefore, the study of the injury mechanism of cardiomyocytes under chronic hypoxia may provide a new treatment strategy for patients with cyanotic coronary heart disease.Mouse cardiomyocytes(CMCs) were treated with hypoxia for different periods of time (oh, 24h, 48h and 72h, respectively), followed by label free proteomic analysis.
2024-06-22 | PXD042055 | Pride
Project description:Tetralogy of Fallot (TOF) is the most commonly seen type of conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation for the failure of cardiac development is lacking for the majority of children with TOF. Our goal was to examine genome wide gene expression to characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot. We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot (16 idiopathic and 3 with 22q11.2 deletions) and compared gene expression patterns to normally developing subjects. We detected a signal from approximately 26,000 probes (ranging from 35% to 49% of array probes in the three tissues), reflecting expression from about half of all genes. More than 1000 genes had a 2-fold change in expression in the right ventricle (RV) of children with TOF compared to RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation). However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, p = 0.017 and Notch, p = 0.003) appeared to be generally suppressed. The suppression of developmental networks may be a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.
2011-01-20 | GSE26125 | GEO
Project description:Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21. Total RNA obtained from DS lymphoblastoid cell lines without congenital heart disease compared to cell lines from DS with congenital heart disease.
2012-08-14 | E-GEOD-34457 | biostudies-arrayexpress