Circulating MicroRNA: Myocardium-Derived Prenatal Biomarker of Ventricular Septal Defects
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA799924 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17715833.fastq.gz | Fastqsanger.gz | |||
| SRR17715834.fastq.gz | Fastqsanger.gz | |||
| SRR17715835.fastq.gz | Fastqsanger.gz | |||
| SRR17715836.fastq.gz | Fastqsanger.gz | |||
| SRR17715837.fastq.gz | Fastqsanger.gz |
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Project description:MicroRNAs (miRNAs) regulate transcription factors and relate to ventricular septal defect (VSD) occurrence, progression and outcome. Recently, circulating miRNAs from maternal blood and amniotic fluid have been used as biomarkers for congenital heart defect (CHD) diagnosis. However, whether circulating miRNAs are associated with foetal heart tissue remains unknown. Dimethadione (DMO) induced a VSD rat model and the miRNA expression profiles of the myocardium, amniotic fluid and maternal serum were analysed. MiRNAs were differentially expressed in the myocardium, amniotic fluid or maternal serum of VSD foetal rats and might be involved in cardiomyocyte differentiation and apoptosis.
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Project description:Right ventricular free wall (RVFW) pacing results in left ventricular dyssynchrony with early septal shortening followed by late lateral contraction that reciprocally stretches the septum. Dyssynchrony is disadvantageous to cardiac mechano-energetics, yet little is known about its molecular consequences. We tested the hypothesis that dyssynchrony selectively alters regional gene expression in mice, employing a novel miniature implantable cardiac pacemaker. Mice were subjected to 1-week overdrive RVFW pacing (720 min-1, baseline HR 520-620 min-1) to induce dyssynchrony (pacemaker: 3V lithium battery, rate programmable, 0.8 grams, bipolar lead). Electrical capture was confirmed by pulsed-wave Doppler at implantation and terminal study, and dyssynchrony by echocardiography. Gene expression from left ventricular septal and lateral-wall myocardium were assessed by microarray (dual-dye method, Agilent) using oligonucleotide probes and dye swap. Identical analysis was applied to 4 synchronously contracting controls. Of 22,000 genes surveyed, only 18 genes displayed significant (p<0.01) differential expression between septal/lateral walls exceeding 1.5-fold relative to any disparities in synchronous controls. These changes were confirmed by qPCR with excellent correlations. Most (16) of the genes showed greater septal expression. Of particular interest were 7 genes coding proteins involved with stretch responses, matrix remodeling, stem cell differentiation to myocyte lineage, and Purkinje fiber differentiation. One-week cardiac dyssynchrony triggers regional differential expression differences in relatively few select genes. Such analysis using a murine implantable pacemaker should facilitate molecular studies of cardiac dyssynchrony and help elucidate novel mechanisms by which stress/stretch stimuli due to dyssynchrony impact the normal and failing heart. Experiment Overall Design: Left ventricle segments from the mouse heart - septal and lateral, were isolated from 4 dyssynchronous mice that were kept separate. RNA from the synchronous mice were pooled into a control septal and lateral sample. Functional genomic analysis was conducted on these 10 RNA samples with fluorophore reversal, such that each sample was assayed on two different microarrays. Corresponding septal and lateral samples from the same heart were paired on the same microarray to measure the relative differences in gene expression between the different regions of the heart then differences were compared across multiple mice to find overlapping genes that were affected by the pacememaker implantation.
2008-06-12 | E-GEOD-3535 | biostudies-arrayexpress
Project description:Ventricular septal defect (VSD) is one of the most prevalent birth defects. The pathogenesis of VSD remains unknown. to analyze the expression of AF-derived lncRNAs and their roles in VSD development, Arraystar Human LncRNA Microarray V5.0 is employed for the global profiling of human lncRNAs and protein-coding transcripts.
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Project description:Objective:This study aims to discover circulating exosomal miRNAs as potential noninvasive biomarkers early detection of fetus with ventricular septal defect (VSD). Method:A total of 182 pregnant women including 91 VSD cases and 91 matched controls were included in this study. Exosomes were isolated and next-generation sequencing was used to obtain a profile of dysregulated exosomal miRNA. The differential abundance was verified by quantitative real-time PCR (q RT-PCR). . Receiver operating characteristic (ROC) curves were conducted to evaluate the diagnostic accucary Results: 77 serum exosomal miRNA were uncovered to be differentially expressed in the VSD group as compared to the control group. Among these, five down-regulated exosomal miRNA were validated by qRT-PCR. hsa-miR-146a-5p was identified to be capable of distinguishing VSDs from controls (area under the ROC (AUC): 0.997; p < 2.2e-16). Conclusion: circulating exosomal miRNA, in particular, hsa-miR-146a-5pmay be a predictive biomarker for non-invasive prenatal diagnosis of fetal VSDs.
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