8e35dae3-3022-40ca-b0c5-78b864825032 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001008952 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:The underlying mechanisms of ventricular remodeling after myocardial infarction (MI) remain largely unknown. Here, we performed an integrative analysis of spatial transcriptomics and single-nucleus RNA-seq in a murine MI model and found that mechanical stress-response genes are expressed at the border zone and play a critical role in left ventricular remodeling following MI. An integrative analysis of single-nucleus RNA-seq and spatial transcriptome of the heart tissue after MI identified the unique cluster that appeared at the border zone in an early stage, highly expressing mechano-sensing genes such as Csrp3. AAV9-mediated gene silencing and overexpression of Csrp3 demonstrated that upregulation of Csrp3 plays critical roles in preventing cardiac remodeling after MI via regulation of genes associated with mechano-sensing. Overall, our study not only provides an insight into spatiotemporal molecular changes following MI but also highlights that the mechano-sensing genes at the border zone act as adaptive regulators of left ventricular remodeling.
2022-07-25 | GSE176092 | GEO
Project description:Introduction: Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by re-establishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Methods: Using a clinically relevant model of IRI, swine were subjected to 45 minutes percutaneous ischemia followed with (MI+HPAC, n=3) or without (MI only, n=3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in non-ischemic, ischemic, and border zone biopsies. Results: Our results established HPAC limited the extent of cardiac injury by 50% (11.02.0% vs 22.03.0%, p=0.039) and preserved ejection fraction in HPAC-treated swine (46.8±2.7% vs 35.8±4.5%, p=0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased anti-apoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. Discussion: We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI.
2023-05-30 | GSE228096 | GEO
Project description:The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI. We evaluated temporal gene expression in a porcine model of myocardial infarction by microarray technology. Nine female pigs (Sus scrofa crossbreed Landrace x Large White) weighing 30-40 kg were subjected to experimental MI by a double-ligation of the first marginal branch of the circumflex artery. Animals were randomly sacrificed at 1 week (n=3), 4 weeks (n=3), or 6 weeks (n=3) after MI. Three paired myocardial samples from the infarct core and remote myocardium were analyzed at each time point. Myocardial samples from sham-operated animals (open-chest cardiac exposure without coronary artery ligation; n=3) were included as physiological controls.
2013-03-01 | E-GEOD-34569 | biostudies-arrayexpress
Project description:Myocardial infarction (MI) is the leading cause for hear failure (HF). Following MI, the non-infarcted region of left ventricle (LV) is critical for maintaining heart function, and disruption of the LV contributes greatly to post-MI HF. Transcriptomic profiling by high-throughput sequencing was performed in a chronic HF pig model, to explore the molecular changes in the post-MI LV related to cardiovascular deterioration. Samples were taken from heart tissue of MI-induced pigs and from control pigs not subjected to MI. Regions of the heart where samples were taken included the site of ischemia (LV ischemia), area bordering ischemia (LV border), area remote to ischemia (LV remote) and the right ventricle (RV).
2021-10-04 | E-MTAB-8856 | biostudies-arrayexpress
Project description:The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI.
2013-03-01 | GSE34569 | GEO
Project description:In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located at the wound border. Here, we show that tomo-seq can be used to identify whole-genome transcriptional profiles of the injury zone, the border zone and the healthy myocardium. Interestingly, the border zone is characterized by the re-expression of embryonic cardiac genes that are also activated after myocardial infarction in mouse and human, including targets of Bone Morphogenetic Protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts. To generate spatially-resolved RNA-seq data for injured zebrafish hearts (3 and 7 days-post-injury), we cryosectioned samples, extracted RNA from the individual sections, and amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing.
2016-01-11 | E-GEOD-74652 | biostudies-arrayexpress
Project description:While the heart regenerates poorly in mammals, efficient heart regeneration occurs in certain amphibian and fish species. Zebrafish has been used extensively to study heart regeneration, resulting in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. However, there is limited knowledge about the cellular processes that occur in this rare population of proliferating cardiomyocytes during heart regeneration. To identify such processes, we generated a transgenic line based on nppa expression that marks proliferating cardiomyocytes located at the wound border zone. Next we have used a single-cell RNA-sequencing approach in the regenerating adult zebrafish heart and we uncovered that proliferating border zone cardiomyocytes have very distinct transcriptomes compared to the non-proliferating remote cardiomyocytes and that they resemble embryonic cardiomyocytes. Moreover, these cells have reduced expression of mitochondrial genes and reduced mitochondrial oxidative phosphorylation activity, while glycolysis gene expression and glucose uptake are increased, indicative for metabolic reprogramming. Mechanistically, this metabolic reprogramming is induced by Nrg1/Erbb2 signaling and this mechanism is conserved in murine hearts. Furthermore, pharmacological inhibition of glycolysis impairs cardiomyocyte proliferation of both zebrafish and murine cardiomyocytes. Together these results reveal a conserved mechanism in which cardiomyocytes undergo metabolic reprogramming, which is essential for cardiomyocyte proliferation and heart regeneration and could ultimately help to develop novel methods to promote mammalian heart repair.
2019-12-24 | GSE139218 | GEO
Project description:The Murphy Roth Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL6/J (C57) mice. The biological processes responsible for this survival advantage are unknown. We compared acute post-MI gene expression in C57 and MRL hearts using microarrays and identified promising candidate biological processes underlying increased survival in the MRL. Hearts from both strains were excised at different time points before or after MI for RNA extraction and hybridization to MOE430A arrays. Baseline hearts were excised from healthy mice that had not undergone the MI procedure (day 0). Infarct tissue in this case means tissue taken from the anterior-apical region that would be the infarct region in a post-MI heart. Non-infarct covers the remainder of the LV. Post-MI hearts were excised either 1 or 5 days after MI. We had successful hybridizations for 3 replicates each of C57 day 0 infarct and non-infarct tissue (6 arrays), 4 MRL day 0 infarct and non-infarct tissue (8 arrays), 4 C57 day 1 infarct and non-infarct tissue (8 arrays), 4 MRL day 1 infarct and non-infarct tissue (8 arrays), 4 C57 day 5 infarct and non-infarct tissue (8 arrays), and 4 MRL day 5 infarct and non-infarct tissue (8 arrays).
2010-05-27 | E-GEOD-19322 | biostudies-arrayexpress
Project description:Closed-chest reperfused MI was induced in pigs by 90-min occlusion, followed by reperfusion of the mid LAD (day 0) and by cardiac MRI with late enhancement (LE) at day 3. At day 30 the animals received either porcine APOSEC (n=8) or placebo medium (n=8) in a randomized manner, injected into the border zone of MI using 3D NOGA percutaneous intramyocardial guidance. At day 60, control cardiac MRI with LE and measurements of myocardial viability via diagnostic NOGA were performed. Gene expression profiling of the infarct core, border zone and normal myocardium was performed using microarray analysis, confirmed by quantitative real-time PCR. Percutaneous endomyocardial injections of APOSEC led to a significant (p<0.05) decrease in infarct size and in improvement of cardiac index and myocardial viability compared to medium treatment. Trend towards higher LV ejection fraction was observed in APOSEC vs. the Medium placebo group (45.4M-BM-15.9% vs 37.4M-BM-18.9%, p=0.052). Transcriptome analysis revealed significant downregulation of caspase-1 and other inflammatory genes in the APOSEC-affected areas. PCR showed higher expression of myogenic factor, Mefc2 (p<0.05) gene with downregulated caspase-3 (p<0.05) in the APOSEC-pigs. We have investigated the effects of catheter-based endomyocardial injections of APOSEC (secretome of apoptotic peripheral white blood cells) on porcine chronic post-infarction (MI) left ventricular (LV) dysfunction and gene expression profile. Pigs randomized to receive eithersecretome (n=8) or medium (placebo control, n=8)
2013-12-31 | E-GEOD-47397 | biostudies-arrayexpress
Project description:Sexual dimorphisms are well recognized in various cardiac diseases, including myocardial infarction (MI). MI develops later in women, but once established, it contributes more persistent symptoms and higher mortality than in men. Although mRNA-level sexual dimorphism of MI have been reported, whether miRNA transcriptome also confers such dimorphism remains unknown. Comprehensive understanding of the mRNA- and miRNA-level genetic programs underlying the heart sexual dimorphisms will expectedly improve clinical outcome by facilitating the development of gender specific treatment strategies. Here, by conducting miRNA microarray analysis of human MI samples, we set out to characterize the heart sexual dimorphisms at the level of miRNA transcriptome Human tissue samples, acquired during post-mortem examination and frozen in liquid nitrogen, were provided by the department of pathology, Tokyo Metropolitan Geriatric Hospital after the approval from the ethical committee. Age- and sex-matched cohorts were selected to compare healthy hearts to those with post-MI LV remodeling. Border zone for myocardial infarction was sampled. Total RNA was extracted using Sepasol solution (Sepasol-RNA I super G, nakalai tesque, Japan), and microarray analysis was performed using Affymetrix GeneChip® miRNA 3.0 Arrays
2016-01-07 | E-GEOD-76591 | biostudies-arrayexpress