Cardiac Mesenchymal Cells from Failing Hearts Limit Ventricular Dilation when Administered Late after Infarction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA602494 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10919415_1.fastq.gz | Fastqsanger.gz | |||
| SRR10919415_2.fastq.gz | Fastqsanger.gz | |||
| SRR10919416_1.fastq.gz | Fastqsanger.gz | |||
| SRR10919416_2.fastq.gz | Fastqsanger.gz | |||
| SRR10919417_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Donor source of cardiac mesenchymal cells influences their expression profile.
2020-09-09 | GSE144010 | GEO
Project description:Although cell therapy-mediated cardiac repair offers promise for treatment/management of heart failure, lack of fundamental understanding of how cell therapy works limits its translational potential. In particular, whether reparative cells from failing hearts differ from cells derived from nonfailing hearts remains unexplored. Here, we assessed differences between cardiac mesenchymal cells (CMC) derived from failing (HF) versus nonfailing (Sham) hearts and whether the source of donor cells (i.e., from HF vs. Sham) limits reparative capacity, particularly when administered late after infarction. To determine the impact of the donor source of CMCs, we characterized the transcriptional profile of CMCs isolated from sham (Sham-CMC) and failing (HF-CMC) hearts. RNA-seq analysis revealed unique transcriptional signatures in Sham-CMC and HF-CMC, suggesting that the donor source impacts CMC. To determine whether the donor source affects reparative potential, C57BL6/J female mice were subjected to 60 min of regional myocardial ischemia and then reperfused for 35 days. In a randomized, controlled, and blinded fashion, vehicle, HF-CMC, or Sham-CMC were injected into the lumen of the left ventricle at 35 days post-MI. An additional 5 weeks later, cardiac function was assessed by echocardiography, which indicated that delayed administration of Sham-CMC and HF-CMC attenuated ventricular dilation. We also determined whether Sham-CMC and HF-CMC treatments affected ventricular histopathology. Our data indicate that the donor source (nonfailing vs. failing hearts) affects certain aspects of CMC, and these insights may have implications for future studies. Our data indicate that delayed administration of CMC limits ventricular dilation and that the source of CMC may influence their reparative actions.NEW & NOTEWORTHY Most preclinical studies have used only cells from healthy, nonfailing hearts. Whether donor condition (i.e., heart failure) impacts cells used for cell therapy is not known. We directly tested whether donor condition impacted the reparative effects of cardiac mesenchymal cells in a chronic model of myocardial infarction. Although cells from failing hearts differed in multiple aspects, they retained the potential to limit ventricular remodeling.
| S-EPMC7474443 | biostudies-literature
Project description:LCMS files from tryptic digests of ~1-4 mg piece of heart ventricular tissue from human with ischemic heart failure and non-failing controls.
Specimen number correspond to .raw files as follows:
Ischemic Heart failure -
54687.1; HF_1_phos.raw
53148.1; HF_2_phos.raw
53589.2; HF_3_phos.raw
54146.1; HF_4_phos.raw
52935.1; HF_5_phos.raw
Non-failing -
52941.1; NHF_1_phos.raw
52777.1; NHF_2_phos.raw
53019.2; NHF_3_phos.raw
53058.1; NHF_4_phos.raw
52621.1; NHF_5_phos.raw
2022-12-07 | MSV000090858 | MassIVE
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:A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing gene expression in ischemic, failing (F) to non-failing (NF) hearts. These results also were compared to the changes observed in a proteomic analysis of F and NF hearts. RNA extracted from the left ventricle was hybridized to Affymetrix arrays to identify gene expression differences in ischemic, end-stage failing versus non-failing hearts. biological replicate: LV_NF_001, LV_NF002, LV_NF004, LV_NF005 biological replicate: LV_F_003, LV_F005, LV_F009, LV_F006
2016-02-08 | E-GEOD-76701 | biostudies-arrayexpress
Project description:Right ventricular dysfunction (RVD) independently predicts worse outcomes in both heart failure (HF) and pulmonary hypertension (PH), irrespective of their etiologies. Yet no evidence-based therapies exist for RVD and progression towards RV failure (RVF) can occur in spite of optimal medical treatment of HF or PH. This disparity reflects our insufficient understanding of the molecular pathophysiology of RVF. To identify molecular mechanisms that may uniquely underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using weighted gene co-expression network and module-phenotype analyses, we identified a 279-member gene module that correlated significantly and specifically with RVF. Within this module, WIPI1 served as a genetic hub, HSPB6, SNAP47, and MAP4 as drivers, and PRDX5 as a repressor of RVF. We subsequently confirmed the ventricular specificity and temporal relationship of Wipi1, Hspb6, and Map4 transcript expression changes in murine models of pressure overload induced RV failure versus LV failure and subsequently uncovered differential dysregulation of autophagy in the failing RV versus the failing LV, namely a shift towards excessive non-canonical, Beclin1-independent, Wipi1/LC3II-mediated autophagy in RVF. In vitro siRNA silencing of Wipi1 partially protected isolated neonatal rat ventricular cardiac myocytes against aldosterone-induced failing phenotype. Moreover, silencing Wipi1 blunted mitochondrial superoxide production and limited non-canonical autophagy in this in vitro RVF model. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and autophagy in cardiac myocytes. Inhibition of Wipi1 may hold promise as a therapeutic target for RVF.
2018-10-05 | GSE120852 | GEO
Project description:Mechanical unloading by ventricular assist devices (VAD) leads to significant gene-expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD-support and its relationship to non-failing hearts (NF). In addition no data are available for the transcriptome regulation during non-pulsatile VAD-support. Therefore we analysed the gene-expression patterns of 30 paired samples from VAD-supported (including 8 non-pulsatile VADs) and 8 non-failing control hearts (NF) using the first total human genome-array available. Transmural myocardial samples were collected for RNA-isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data was analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). 352 transcripts were differentially regulated between samples from VAD-implantation and NF, whereas 510 were significantly regulated between VAD-transplantation and NF (paired t-test p<0.001, fold change >=1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD-support. Unsupervised hierarchical clustering of paired VAD- and NF-samples revealed separation of HF- and NF- samples, however individual differentiation of VAD-implantation and VAD-transplantation was not accomplished. Clustering of pulsatile and non-pulsatile VAD did not lead to robust separation of gene expression patterns. During VAD-support myocardial gene expression changes do not indicate reversal of the HF-phenotype, but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and non-pulsatile VAD-supported hearts did not provide evidence for a pump-mode specific transcriptome pattern. Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from end-stage heart failure pre and post mechanical unloading.
2010-07-29 | E-GEOD-21610 | biostudies-arrayexpress
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. Total RNA from the LA and LV of failing male (n=9), failing female (n=7), nonfailing male (n=9), and nonfailing female (n=9) hearts was probed using a custom-designed Taqman gene array from Applied Biosystems. Tissues from LA (n=22), LV (n=22), LV endocardium (n=12), and LV epicardium (n=12) were analyzed by the Applied Biosystems SDS 2.3 software using the threshold cycle (Ct) relative quantification method with GAPDH as an endogenous control.
2012-02-01 | E-GEOD-33165 | biostudies-arrayexpress
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: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.
2011-11-30 | GSE29819 | GEO