Spatial Transcriptional Landscape of Human Heart Failure
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE271676 | GEO | 2025/05/08
REPOSITORIES: GEO
Similar Datasets
Project description:In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and adult mice with HF. Our screen identified 5-oxoprolinase (OPLAH), a member of the -Glutamyl cycle, that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients we observed elevated plasma 5-oxoproline levels, which were associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential novel diagnostic, prognostic and therapeutic options in HF.
2017-11-08 | E-MTAB-5449 | biostudies-arrayexpress
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:Full Title: Transition from Compensated Hypertrophy to Systolic Heart Failure in the Spontaneously Hypertensive Rat: Structure, Function, and Transcript Analysis Gene expression changes and left ventricular remodeling associated with the transition to systolic heart failure (HF) were determined in the spontaneously hypertensive rat (SHR). By combining transcriptomics of left ventricles from six SHR with HF with changes in function and structure we aimed to better understand the molecular events underlying the onset of systolic HF compared to six age-matched, SHR with compensated hypertrophy. Left ventricle (LV) ejection fraction was depressed (82±4 to 52±3 %) in compensated vs. failing animals. Systolic blood pressure decreased and LV end-diastolic and systolic volume increased with HF. Failing SHR hearts also demonstrated increases in left and right ventricular mass relative to non-failing SHRs.  LV papillary muscle force development and shortening velocity decreased, β-adrenergic responsiveness was depressed, myocardial stiffness and myocardial fibrosis increased with HF relative to non-failing animals. Initial micro-array analysis revealed that 1,431 transcripts were differentially expressed with HF compared to non-failing SHR (p<0.05). Of the identified transcripts, lipopolysaccharide binding protein, the most highly expressed transcript with HF, was negatively correlated to myocardial force while elevated expression of the collagen cross-linking enzyme lysyl oxidase correlated positively with muscle stiffness. Besides these individual transcripts, gene set enrichment analysis (GSEA) identified multiple enriched pathways with HF, most prominent of the altered signaling pathways involved TGF-β and insulin signaling. GESA analysis additionally identified altered gene sets involving inflammation, oxidative stress, cell degradation and cell death, among others (all p<0.01). In contrast to diastolic HF where few transcripts are reported to be altered, our data indicate multiple genes and pathways involved in a variety of biological processes characterize the onset of systolic HF, consistent with many functional and structural changes present in the failing hypertensive heart. Comprehensive gene expression profiling of heart failure Rat model vs control.
2010-02-21 | E-GEOD-19210 | biostudies-arrayexpress
Project description:Full Title: Transition from Compensated Hypertrophy to Systolic Heart Failure in the Spontaneously Hypertensive Rat: Structure, Function, and Transcript Analysis Gene expression changes and left ventricular remodeling associated with the transition to systolic heart failure (HF) were determined in the spontaneously hypertensive rat (SHR). By combining transcriptomics of left ventricles from six SHR with HF with changes in function and structure we aimed to better understand the molecular events underlying the onset of systolic HF compared to six age-matched, SHR with compensated hypertrophy. Left ventricle (LV) ejection fraction was depressed (82±4 to 52±3 %) in compensated vs. failing animals. Systolic blood pressure decreased and LV end-diastolic and systolic volume increased with HF. Failing SHR hearts also demonstrated increases in left and right ventricular mass relative to non-failing SHRs. LV papillary muscle force development and shortening velocity decreased, β-adrenergic responsiveness was depressed, myocardial stiffness and myocardial fibrosis increased with HF relative to non-failing animals. Initial micro-array analysis revealed that 1,431 transcripts were differentially expressed with HF compared to non-failing SHR (p<0.05). Of the identified transcripts, lipopolysaccharide binding protein, the most highly expressed transcript with HF, was negatively correlated to myocardial force while elevated expression of the collagen cross-linking enzyme lysyl oxidase correlated positively with muscle stiffness. Besides these individual transcripts, gene set enrichment analysis (GSEA) identified multiple enriched pathways with HF, most prominent of the altered signaling pathways involved TGF-β and insulin signaling. GESA analysis additionally identified altered gene sets involving inflammation, oxidative stress, cell degradation and cell death, among others (all p<0.01). In contrast to diastolic HF where few transcripts are reported to be altered, our data indicate multiple genes and pathways involved in a variety of biological processes characterize the onset of systolic HF, consistent with many functional and structural changes present in the failing hypertensive heart.
2010-02-01 | GSE19210 | GEO
Project description:Increased morbidity and mortality associated with post-ischemic heart failure (HF) in diabetic patients underscore the need for a better understanding of the underlying molecular events. Indeed, effective HF therapy in diabetic patients requires a complex strategy encompassing the development of improved diagnostic and prognostic markers and innovative pharmacological approaches. Whole mRNAs expression was measured in the heart of patients with heart failure (HF) with or without concomitant Type 2 diabetes mellitus (T2DM) and compared it to control non-failing hearts. We identified distinct genes modulated in HF patients compared to controls, as well as to T2DM HF patients compared to not diabetic HF patients.
2012-03-21 | GSE26887 | GEO
Project description:Heart failure (HF) is a major global problem with increasing numbers of patients and deaths in many countries. Existing studies on HF have focused primarily on cardiomyocytes, with few studies targeting non-cardiomyocytes. This study focused on cardiac fibroblasts (CFs) as a cause of HF. Single-cell RNA sequencing of mouse hearts revealed six distinct subclusters of CFs at various stages after pressure overload, with one subcluster being specific to the HF stage. The transcription factor c-Myc is specifically expressed in HF-specific CFs. CFs-specific deletion of c-Myc ameliorates pressure overload-induced cardiac dysfunction without affecting fibrosis. The chemokine Cxcl1 is highly expressed in HF-specific CFs and downregulated in CFs-specific c-Myc knockout mice. Chromatin immunoprecipitation analysis revealed that c-Myc binds to the promoter region of Cxcl1 in CFs. Cxcr2, the receptor for Cxcl1, is expressed in cardiomyocytes, and blockade of the Cxcl1-Cxcr2 signalling pathway prevents pressure overload-induced cardiac dysfunction. The addition of CXCL1 reduces the contractility of cardiomyocytes of neonatal rats and human iPS-derived cardiomyocyte organoids. Human CFs from failing hearts expressed c-MYC and CXCL1, while CFs from control hearts did not. These findings suggest that HF-specific CFs play an important role in inducing HF by upregulating c-Myc and Cxcl1 and that CFs could be a novel therapeutic target for HF.
2025-07-18 | GSE302337 | GEO
Project description:Heart failure (HF) is driven via interplay between master regulatory transcription factors and dynamic alterations in chromatin structure. While pathologic gene transactivation in this context is known to be associated with recruitment of histone acetyl-transferases and local chromatin hyperacetylation, the role of epigenetic reader proteins in cardiac biology is unknown. We therefore undertook a first study of acetyl-lysine reader proteins, or bromodomains, in HF. Using a chemical genetic approach, we establish a central role for BET-family bromodomain proteins in gene control during HF pathogenesis. BET inhibition potently suppresses cardiomyocyte hypertrophy in vitro and pathologic cardiac remodeling in vivo. Integrative transcriptional and epigenomic analyses reveal that BET proteins function mechanistically as pause-release factors critical to activation of canonical master regulators and effectors that are central to HF pathogenesis and relevant to the pathobiology of failing human hearts. This study implicates epigenetic readers in cardiac biology and identifies BET co-activator proteins as therapeutic targets in HF. Gene expression analysis of mouse hearts subjected to either trans aortic constriction (TAC) or sham surgeries followed by treamtent with dmso vehicle or the BET bromodomain inhibitor JQ1
2013-08-06 | E-GEOD-48110 | biostudies-arrayexpress
Project description:The goal of this experiment was to identify gene expression changes that are common in different heart failure (HF) types or specific to an etiology of HF. HF groups studied include doxorubicin induced cardiomyopathy, familial dilated cardiomyopathy, hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy, ischemic heart disease, peripartum cardiomyopathy, and viral induced cardiomyopathy. Non-diseased left ventricles (LV) were obtained from donor hearts not used for transplantation (these were considered to be unsuitable for transplantation for a variety of reasons including the lack of a tissue-compatible recipient). Failing LV were obtained from patients undergoing heart transplantation. Transmural sections of LV anterior free wall were trimmed of fat, dissected into 1-1.5 gm pieces, and immediately frozen in the operating theater. 100-200 mg of frozen transmural LV was ground to a fine powder in liquid nitrogen using a mortar and pestle. Then total RNA was isolated by a method described by Wei and Khan (A Molecular Cloning Manual). The purity of the RNA extract was assessed by measuring the absorbance at 260 nm and 280 nm. Its quantity and integrity was then examined using RNA Nano Chips on a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA, USA). 10 ?g of RNA extracts and a universal human reference RNA (Stratagene, La Jolla, CA, USA) were reverse transcribed with Cy3-dUTP and Cy5-dUTP, respectively, to produce labeled cDNA probes using Thermoscript reverse transcriptase according Hwang JJ et. al. (Physiological Genomics 10: 31-44, 2002). Raw scanned images were processed using ScanAlyze version 2.50 (Michael Eisen, Stanford University, CA, USA). Cy3 and Cy5 scans were superimposed, local backgrounds were subtracted, and the fluorescence intensities of each spot were quantified. All further analyses of CardioChips were done using GeneSpring version 6.1 (Silicon Genetics, Redwood City, CA, USA). The data from each array was normalized first to the reference RNA and then a LOWESS curve was fit to the log-intensity versus log-ratio plot for each array and for each gene across all experiments. 40.0% of the data was used to calculate the LOWESS fit at each point. Differentially expressed genes in each HF group compared to donor hearts were identified by a one-way ANOVA test (P <0.05) with the benjamini and hochberg multiple testing corrections and we selected those genes with an average difference greater than 1.5 fold. A hierarchical clustering analysis was performed using pearson correlation with the separation ratio of 1.0 and minimum distance of 0.001 as similarity measure. Using a cardiovascular-specific gene array (CardioChip) of 42 heart failure (HF) patients from a wide range of etiology groups and 8 non-failing donors, we have identified down-regulation of LIM domain protein which may be an important pathway for the clinical progression of HF. We identified six genes, encoding LIM domain and Homer proteins, that are down-regulated in terminally failing hearts. The LIM and cysteine rich domain 1 (LMCD1) gene, in particular, was significantly down-regulated in all HF samples. This novel finding suggests that the LMCD 1 is a universal biomarker for end-stage HF. Other LIM domain genes were also down-regulated but only in non-familial dilated forms of cardiomyopathy. This is probably due to the fact that down-regulation of LIM protein expression may disrupt the cytoskeletal architecture, leading to dilated cardiomyopathy. In addition to identifying the LIM domain genes as possible regulatory genes involved in HF, we also demonstrated that the gene expression profile was able to classify multiple HF patients groups. This paper is the first to examine viral-induced cardiomyopathy, doxorubicin toxicity cardiomyopathy and perimartum cardiomyopathy and to perform the clustering analysis of those HF types providing new insights into human HF.
2010-06-10 | E-GEOD-2656 | biostudies-arrayexpress
Project description:Sinoatrial node (SAN), and right atrial (RA) fibroblasts were isolated from explanted non-failing (nHF) and HF human hearts, cultured, passaged once, and treated +/- transforming growth factor beta 1(TGF beta-1). Fibroblast pellets were subjected to comprehensive high-throughput proteomic analyses.
2021-01-12 | MSV000086692 | MassIVE
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.
2010-05-20 | GSE21610 | GEO