Similar Datasets
Project description:Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Lysine demethylase 8 (Kdm8) represses gene expression in the embryo and controls metabolism in cancer. However, its function in cardiac homeostasis is unknown. We show that Kdm8 maintains a mitochondrial gene network active by repressing Tbx15 to prevent dilated cardiomyopathy leading to lethal heart failure. Deletion of Kdm8 in mouse cardiomyocytes increased H3K36me2 with activation of Tbx15 and repression of target genes in the NAD+ pathway before dilated cardiomyopathy initiates. Moreover, NAD+ supplementation prevented dilated cardiomyopathy in Kdm8 mutant mice and TBX15 overexpression blunted NAD+-activated cardiomyocyte respiration. Furthermore, KDM8 was downregulated in human hearts affected by dilated cardiomyopathy and higher TBX15 expression defines a subgroup of affected hearts with the strongest downregulation of genes encoding mitochondrial proteins. Thus, KDM8 represses TBX15 to maintain cardiac metabolism. Our results suggest that epigenetic dysregulation of metabolic gene networks initiates myocardium deterioration towards heart failure and could underlie heterogeneity of dilated cardiomyopathy.
2022-12-23 | GSE215793 | GEO
Project description:Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Lysine demethylase 8 (Kdm8) represses gene expression in the embryo and controls metabolism in cancer. However, its function in cardiac homeostasis is unknown. We show that Kdm8 maintains a mitochondrial gene network active by repressing Tbx15 to prevent dilated cardiomyopathy leading to lethal heart failure. Deletion of Kdm8 in mouse cardiomyocytes increased H3K36me2 with activation of Tbx15 and repression of target genes in the NAD+ pathway before dilated cardiomyopathy initiates. Moreover, NAD+ supplementation prevented dilated cardiomyopathy in Kdm8 mutant mice and TBX15 overexpression blunted NAD+-activated cardiomyocyte respiration. Furthermore, KDM8 was downregulated in human hearts affected by dilated cardiomyopathy and higher TBX15 expression defines a subgroup of affected hearts with the strongest downregulation of genes encoding mitochondrial proteins. Thus, KDM8 represses TBX15 to maintain cardiac metabolism. Our results suggest that epigenetic dysregulation of metabolic gene networks initiates myocardium deterioration towards heart failure and could underlie heterogeneity of dilated cardiomyopathy.
2022-12-23 | GSE215351 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-16 | GSE241120 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-17 | GSE142129 | GEO
Project description:To investigate the physiological characteristics of cardiac fibroblasts (CF) from pediatric dilated cardiomyopathy (DCM) patients, CFs were harvested from left ventricular free wall at the heart transplantation. We then performed RNA-seq for 7 different lines of CFs.
2023-09-12 | GSE223517 | GEO
Project description: Not available
| S-EPMC8160050 | biostudies-literature
Project description:BackgroundGenetic studies of cardiomyopathy and heart failure have limited throughput in mammalian models. Adult zebrafish have been recently pursued as a vertebrate model with higher throughput, but genetic conservation must be tested.Methods and resultsWe conducted transcriptome analysis of zebrafish heart and searched for fish homologues of 51 known human dilated cardiomyopathy-associated genes. We also identified genes with high cardiac expression and genes with differential expression between embryonic and adult stages. Among tested genes, 30 had a single zebrafish orthologue, 14 had 2 homologues, and 5 had ≥3 homologues. By analyzing the expression data on the basis of cardiac abundance and enrichment hypotheses, we identified a single zebrafish gene for 14 of 19 multiple-homologue genes and 2 zebrafish homologues of high priority for ACTC1. Of note, our data suggested vmhc and vmhcl as functional zebrafish orthologues for human genes MYH6 and MYH7, respectively, which are established molecular markers for cardiac remodeling.ConclusionsMost known genes for human dilated cardiomyopathy have a corresponding zebrafish orthologue, which supports the use of zebrafish as a conserved vertebrate model. Definition of the cardiac transcriptome and fetal gene program will facilitate systems biology studies of dilated cardiomyopathy in zebrafish.
| S-EPMC4406804 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-09-30 | GSE243740 | GEO
Project description:Metabolomics can be performed either as an 'open profiling' tool where the aim is to measure, usually in a semi-quantitative manner, as many metabolites as possible or perform 'closed' or 'targeted' analyses where instead a pre-defined set of metabolites are measured. Targeted methods can be designed to be more sensitive and quantitative and so are particularly appropriate to systems biology for quantitative models of systems or when metabolomics is performed in a hypothesis driven manner to test whether a particular pathway is perturbed. We describe a targeted metabolomics assay that quantifies a broad range of over 130 metabolites relevant to cardiac metabolism including the pathways of the citric acid cycle, fatty acid oxidation, glycolysis, the pentose phosphate pathway, amino acid metabolism, the urea cycle, nucleotides and reactive oxygen species using tandem mass spectrometry to produce quantitative, sensitive and robust data. This assay is illustrated by profiling cardiac metabolism in a lamin A/C (Lmna) mouse model of dilated cardiomyopathy (DCM). The model of DCM was characterised by increases in concentrations of proline and methyl-histidine suggestive of increased myofibrillar and collagen degradation, as well as decreases in a number of citric acid cycle intermediates and carnitine derivatives indicating reduced energy metabolism in the dilated heart. These assays could be used for any other cardiac or cardiovascular disease in that they cover central core metabolism and key pathways involved in cardiac metabolism, and may provide a general start for many mammalian systems.
| S-EPMC4781888 | biostudies-other
Project description:This project analyzes genome-wide cardiac DNA methylation in patients with idopathic DCM and control individuals Given are datafiles from n = 8 controls (patients after Htx) and n = 9 patients with idopathic DCM. The datasets have been normalized together with other beadchip files not subject to this study. Methylation profiles were generated from human left ventricular myocardium DNA.
2012-12-18 | E-GEOD-42510 | biostudies-arrayexpress