Changes in molecular profiles of the left ventricle during progressive dilated cardiomyopathy linked heart failure
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE225008 | GEO | 2023/06/29
REPOSITORIES: GEO
Similar Datasets
Project description:Cardiomyopathies are heart muscle disorders characterised by chamber dilation often accompanied by wall thinning, severe systolic and diastolic dysfunction and frequently heart failure. Although several genes were found to be differentially expressed the cellular and molecular basis of the disease still remains poorly understood. We performed expression profiling on cardiac samples from six different mouse disease models: muscle LIM protein- (MLP), ErbB2-, ErbB4- and plakoglobin-deficient mice, doxorubicin treated mice and doxorubicin treated ErbB4 deficient mice. We aimed at the identification of general cardiomyopathy expression patterns as well as mouse model specific ones. Keywords: expression profiling, mouse models for cardiomyopathy
2008-05-01 | GSE7746 | GEO
Project description:Analysis of the effects of aging on the development of dilated cardiomyopathy by characterizing both changes in ejection fraction (EF) and gene expression profile in 3 groups of male mice: Control (Cont or WT, n=11) and transgenic (Tg or KO) mice with either high EF (KO-H or Tg-H, n=7) or low EF (KO-L or Tg-L, n=6). We previously produced a line of transgenic mice (Tg) on a mixed genetic background where cardiac-specific overexpression of Cre recombinase reduced expression of the EP4 receptor gene. There were no obvious phenotypes in 10-12-week-old male Tg mice. To determine if a cardiac phenotype developed in aged mice, we assessed cardiac structure and function by echocardiography, histology and gene expression in 23-33-week-old male Tg and littermates (Cont). After echocardiography, hearts were removed to assess hypertrophy (MCSA), fibrosis (ICF) and macrophage infiltration by histological methods and for extraction of total RNA and protein. Cont mice had a normal EF of 80±0.6% (n=70), whereas Tg mice had a lower EF (60±2.7%, n=55, p<0.001) coupled with left ventricular dilatation. The distribution of EFs in the Tg mice was large, ranging from normal to below 30%. MCSA and infiltrating macrophages were not different between groups, but ICF increased by 35% in Tg mice. Cre protein levels in heart lysates did not correlate with either age or EF. In contrast to male Tg mice, female Tg mice had no cardiac dysfunction assessed by echocardiography from 12 to 28 weeks of age. To understand gene expression differences between Cont and Tg mice, whole genome gene expression profiling (Illumina BeadChips) on hearts of 30-32 week old male mice was done. Data indicated that 595 genes were overexpressed in the Tg hearts, 156 of which changed more than 2-fold, including genes involved in remodeling, inflammation, and oxidative stress. 512 genes were downregulated in the Cont hearts, 79 of which changed more than 2-fold, including genes involved with calcium handling, K+ channels, and fatty acid transport and metabolism. In conclusion, Cre overexpression and EP4 knock down in cardiac myocytes in aged male but not female Tg mice are in part associated with increased fibrosis, reduced EF and dilated cardiomyopathy; however, Cre protein itself does not seem to be responsible for the cardiomyopathy. The absence of cardiac dysfunction in female mice suggests a sexual dimorphism in the phenotype. Creation of the cardiac-myocyte specific EP4 KO mouse and littermate controls was described in JY Qian et al, Hypertension 2008: 51(pt 2):560-566. Total RNA extracted from left ventricle of control (Cont or WT, n =11) and cardiac-specific EP4 KO (Tg or KO, n=13) male mice (mean age 31 weeks).
2010-04-13 | E-GEOD-16909 | biostudies-arrayexpress
Project description:The IGF2BP family of RNA binding proteins consists of three paralogs, IGF2BP1, 2, and 3, that regulate RNA function at many levels, including intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. Several previous studies indicated that IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodelling and returns to normal levels in recovering hearts. These results suggested that IGF2BP2 might play an adaptive role during cardiac stress and recovery. To investigate the role of IGF2BP2 in the heart, we made use of a conditional, inducible transgenic mouse line. Enhanced expression of the IGF2BP2 transgene in hearts of newborn or adult mice leads to dilated cardiomyopathy (DCM), with remodelling, fibrosis, and death occurring within 3-4 weeks. Turning off expression of the transgene after 2 weeks, however, rescues these mice, and they recover completely by 12 weeks. Proteomic analysis identified a downregulation of sarcomeric and mitochondrial proteins in hearts overexpressing IGF2BP2, and electron microscopy revealed fragmented mitochondria and elongated, thinner sarcomeres, suggesting a possible mechanism of action. Consistent with these results, IGF2BP2 is upregulated in patients with DCM or after myocardial infarction. These results show that cardiac stress upregulates IGF2BP2, and this upregulation causes remodelling and compensation of the heart. Prolonged IGF2BP2 expression, however, leads to heart failure and death, making it an attractive target for therapeutic intervention.
2024-01-26 | PXD037623 | Pride
Project description:Mice heterozygous for dn-p21 littermates were sacrificed at 10 weeks of age. Ventricles were isolated and snap-frozen in liquid nitrogen. Use 3 month old FVB Females as controls. [GSM2334, GSM2335, GSM2336] Read more at http://cardiogenomics.med.harvard.edu/groups/proj1/pages/ras_home.html Keywords = ras Keywords = dilated cardiomyopathy Keywords: other
2003-10-24 | GSE760 | GEO
Project description:Analysis of the effects of aging on the development of dilated cardiomyopathy by characterizing both changes in ejection fraction (EF) and gene expression profile in 3 groups of male mice: Control (Cont or WT, n=11) and transgenic (Tg or KO) mice with either high EF (KO-H or Tg-H, n=7) or low EF (KO-L or Tg-L, n=6). We previously produced a line of transgenic mice (Tg) on a mixed genetic background where cardiac-specific overexpression of Cre recombinase reduced expression of the EP4 receptor gene. There were no obvious phenotypes in 10-12-week-old male Tg mice. To determine if a cardiac phenotype developed in aged mice, we assessed cardiac structure and function by echocardiography, histology and gene expression in 23-33-week-old male Tg and littermates (Cont). After echocardiography, hearts were removed to assess hypertrophy (MCSA), fibrosis (ICF) and macrophage infiltration by histological methods and for extraction of total RNA and protein. Cont mice had a normal EF of 80±0.6% (n=70), whereas Tg mice had a lower EF (60±2.7%, n=55, p<0.001) coupled with left ventricular dilatation. The distribution of EFs in the Tg mice was large, ranging from normal to below 30%. MCSA and infiltrating macrophages were not different between groups, but ICF increased by 35% in Tg mice. Cre protein levels in heart lysates did not correlate with either age or EF. In contrast to male Tg mice, female Tg mice had no cardiac dysfunction assessed by echocardiography from 12 to 28 weeks of age. To understand gene expression differences between Cont and Tg mice, whole genome gene expression profiling (Illumina BeadChips) on hearts of 30-32 week old male mice was done. Data indicated that 595 genes were overexpressed in the Tg hearts, 156 of which changed more than 2-fold, including genes involved in remodeling, inflammation, and oxidative stress. 512 genes were downregulated in the Cont hearts, 79 of which changed more than 2-fold, including genes involved with calcium handling, K+ channels, and fatty acid transport and metabolism. In conclusion, Cre overexpression and EP4 knock down in cardiac myocytes in aged male but not female Tg mice are in part associated with increased fibrosis, reduced EF and dilated cardiomyopathy; however, Cre protein itself does not seem to be responsible for the cardiomyopathy. The absence of cardiac dysfunction in female mice suggests a sexual dimorphism in the phenotype. Creation of the cardiac-myocyte specific EP4 KO mouse and littermate controls was described in JY Qian et al, Hypertension 2008: 51(pt 2):560-566.
2010-03-31 | GSE16909 | GEO
Project description:Background: The p.(Arg14del) pathogenic variant (R14del) of the phospholamban (PLN) gene is a prevalent cause of cardiomyopathy with heart failure. The exact underlying pathophysiology is unknown, and a suitable therapy is unavailable. We aim to identify molecular perturbations underlying this cardiomyopathy in a clinically relevant PLN-R14del mouse model. Methods: We investigated progression of cardiomyopathy in PLN-R14∆/∆ mice using echocardiography, electrocardiography and histological tissue analysis. RNA sequencing and mass spectrometry were performed on cardiac tissues at 3 weeks of age (before onset of disease), 5 weeks, when mild cardiomyopathy has developed, and 8 weeks (end-stage). Data were compared with cardiac expression levels of mice that underwent myocardial ischemia-reperfusion or myocardial infarction surgery, in an effort to identify alterations that are specific to PLN-R14del-related cardiomyopathy. Results: At 3 weeks of age, PLN-R14∆/∆ mice had normal cardiac function, but from the age of 4 weeks, we observed increased myocardial fibrosis and impaired global longitudinal strain. From 5 weeks onwards, ventricular dilatation, decreased contractility and diminished ECG voltages were observed. Strikingly, PLN protein aggregation was present prior to onset of functional deficits. Transcriptomics and proteomics revealed differential regulation of processes involved in remodelling, inflammation and metabolic dysfunction, in part similar to ischemic cardiomyopathy. Protein homeostasis pathways were identified exclusively in PLN-R14∆/∆ mice, even before disease onset, in concert with aggregate formation. Conclusions: We mapped the development of PLN-R14del-related cardiomyopathy, and identified alterations in proteostasis and PLN protein aggregation amongst the first manifestations of this disease, which could possibly be a novel target for therapy.
2021-11-03 | PXD024594 | Pride
Project description:Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. To test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cε (PKCε) mouse model of DCM. Transgenic mice expressing constitutively active PKCε in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to heart failure, cardiac fibrosis, and increased mortality. Beginning at 3 months of age, mice were treated with an antibody to CTGF (FG-3149) or non-immune IgG control antibody for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKCε mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKCε mice, but significantly decreased by CTGF inhibition, however total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCε mice suggests that CTGF inhibition may benefit patients with DCM. Total RNA was isolated from the left ventricle of 6-month-old PKCε transgenic mice or nontransgenic FVB/N controls 3 months after initiation of treatment with IgG (n=10 biological replicates each) or anti-CTGF antibody FG-3149 (n=12 each) and hybridized to Affymetrix 430A 2.0 microarrays. CEL files were processed by GCRMA and rescaled using median per-gene normalization in GeneSpring GX 7.3.1.
2015-11-20 | E-GEOD-68857 | biostudies-arrayexpress
Project description:Analysis of heart from myocardil specific deletion of Jarid2 by crossing Jarid2 floxed mice with aMHC-Cre mice (Jarid2-aMHC). Jarid2-aMHC mice regult in dilated cardomyopathy and reveal premature death. To identify differentially expressed genes in Jarid2-aMHC hearts, we performed RNA-seq analysis on mutant hearts and control heart at postnatal day 10 (P10) and 7 months of ages (7M).
2018-08-23 | GSE118945 | GEO
Project description:This study attempts at investigating the changes in cardiac gene expression that occur in Dilated Cardiomyopathy (DCM). DCM in Dobermans and Boxers are the focus of this study. Control heart tissue as well as Pacing tissue used is from mongrel dogs. Keywords: control vs pacing vs disease; strain specific disease 3 Dobermans-DCM, 4 Boxers-DCM, 3 mongrels-control and 3 mongrels-pacing
2008-05-08 | E-GEOD-11015 | biostudies-arrayexpress
Project description:Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. To test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cε (PKCε) mouse model of DCM. Transgenic mice expressing constitutively active PKCε in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to heart failure, cardiac fibrosis, and increased mortality. Beginning at 3 months of age, mice were treated with an antibody to CTGF (FG-3149) or non-immune IgG control antibody for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKCε mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKCε mice, but significantly decreased by CTGF inhibition, however total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCε mice suggests that CTGF inhibition may benefit patients with DCM.
2015-11-20 | GSE68857 | GEO