Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome dynamics during the development of heart failure caused by mitochondrial complex I dysfunction and pressure overload

ABSTRACT: Comprehensive knowledge of the dynamic changes in the cardiac transciptome can inform disease mechanism. Previous transcriptome profiling studies on heart failure rely on either microarray or RNA-Seq with low coverage, leaving a large portion of the transcriptome unexplored. Additionally, previous studies only examined two end stages of the disease, onset and late-stage heart failure. Profile of the transcriptome in the middle stage of disease progression can reveal critical molecular events underlying disease transition. Towards these goals, we conducted a multi-factorial RNA-Seq experiment, comparing the dynamic changes in the transcriptome of two murine models of heart failure, pressure overload and loss of mitochondrial complex I. Our data represents the deepest transcriptome coverage to date, covering onset, progression, and late stage of the disease. We found extensive differences in the expression magnitude and dynamics of the transciptomes in different heart failure models. In addition, such differences are associated with progressive worsening of cardiac physiology. Our analysis revealed that mitochondrial dysfunction combined with stress leads to increased number of differentially expressed long intergenic noncoding RNAs, including a recently identified lincRNA that is a master regulator of the cardiac lineage during development.

ORGANISM(S): Mus musculus

PROVIDER: GSE66630 | GEO | 2016/12/09

SECONDARY ACCESSION(S): PRJNA277489

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CIP, a cardioprotective factor, inhibits the transition from cardiac hypertrophy to heart failure

Project description:Heart failure is characterized by the inability of the heart to pump effectively and generate proper blood circulation to meet the body's needs; it is a devastating condition that affects more than 100 million people globally. In spite of this, little is known about the mechanisms regulating the transition from cardiac hypertrophy to heart failure. Previously, we identified a cardiomyocyte-enriched gene, CIP, which regulates cardiac homeostasis under pathological stimulation. Here, we show that the cardiac transcriptional factor GATA4 binds the promotor of CIP gene and regulates its expression. We further determined that both CIP mRNA and protein decrease in diseased human hearts. In a mouse model, induced cardiac-specific overexpression of CIP after the establishment of cardiac hypertrophy protects the heart by inhibiting disease progression toward heart failure. Transcriptome analyses revealed that the IGF, mTORC2 and TGFβ signaling pathways mediate the inhibitory function of CIP on pathologic cardiac remodeling. Our study demonstrates GATA4 as an upstream regulator of CIP gene expression in cardiomyocytes, as well as the clinical significance of CIP expression in human heart disease. More importantly, our investigation suggests CIP is a key regulator of the transition from cardiac hypertrophy to heart failure. The ability of CIP to intervene in the onset of heart failure suggests a novel therapeutic avenue of investigation forthe prevention of heart disease progression.

2022-03-05 | GSE194149 | GEO

Single cell sequencing of mouse heart immune infiltrate in pressure overload-driven heart failure reveals extent of immune activation

Project description:Single-cell RNA sequencing is revolutionizing the mapping of tissues in physiology and pathology. Whilst immune responses are emerging as key mediators of heart failure, no thorough immune mapping of the ailing heart has been performed so far. Here we examined, at single-cell level, the cardiac immune composition after transverse aortic constriction, the standard murine model of non-ischemic heart failure. We identified the presence of most major immune cell subpopulations in the myocardium of both healthy and cardiopathic mice. Despite the absence of infectious agents or an autoimmune trigger, the ailing heart, especially at late-stage disease, is characterized by an immune activation that is both drastic and far more wide-ranging in the immune cell types involved than previously thought. The molecular-level detail we uncover in the cells undergoing activation in response to cardiac stress may enable the identification of novel biomarkers and therapeutic targets for heart failure.

2019-10-12 | GSE122930 | GEO

Single-cell analysis revealed the role of CD8+ effector T cells in preventing cardioprotective macrophage differentiation in the early phase of heart failure

Project description:Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. It has been characterized that heart resident and infiltrated macrophages play important roles in the cardiac remodeling in response to cardiac pressure overload, however, role of T cells has not been well characterized. Here we show that CD8+T cell depletion resulted in the late stage heart protection, but induced cardioprotective hypertrophy at an early stage of heart failure caused by cardiac pressure overload. Single cell RNA sequencing analysis revealed that cardioprotective hypertrophy was characterized by an expression of mitochondrial genes and growth factor receptors genes. CD8+T cells regulated the conversion of cardiac-resident macrophages as well as infiltrated macrophages to cardioprotective macrophages which express growth factor genes including Areg, Osm and Csf1 at the early phase of cardiac pressure overload, which are essential for the myocardial adaptive response. Our results demonstrate a dynamic interplay between cardiac CD8+T cells and macrophages that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages.

2021-10-04 | GSE183024 | GEO

Microarray gene expression profiling of cardiac genes at the onset of heart failure

2010-12-03 | GSE25765 | GEO

RNA-Sequencing shows novel transcriptomic signatures in failing and non-failing human heart

Project description:The knowledge of an expression network signature in end-stage heart failure (HF) diseased hearts may offer important insights into the complex pathogenesis of advanced cardiac failure, as well as it may provide potential targets for therapeutic intervention. In this study, the NGS sequencing of RNA (RNA-Seq) method was employed to obtain the whole transcriptome of cardiac tissues from transplant recipients with advanced stage of HF. The analysis of RNA-Seq data presents novel challenges and many methods have been developed for the purpose of mapping reads to genomic features and quantifying gene expression. The main goal of this work was to identify, characterize and catalogue all the transcripts expressed within cardiac tissue and to quantify the differential expression of transcripts in both physio- and pathological conditions through whole transcriptome analyses. Expression levels, differential splicing, allele-specific expression, RNA editing and fusion transcripts constitute important information when comparing samples for disease related studies. Analysis methods for RNA-Seq data are continuing to evolve. Thus, in order to find the best solution for filter generated list of differentially expressed genes, an informatic approach of NOISeq BIO method has been applied in this RNA-Seq analysis. Most of the genes obtained by filtering differentially expressed gene list, have been experimentally validated by Real time RT-PCR. Noteworthy, these findings provide valuable resources for further studies of the molecular mechanisms involved in heart ischemic response thus leading to potential novel biomarkers and targets for therapeutic intervention in the onset and progression of cardiomyopathies. Heart biopsies from candidates for solid organ transplantation were collected and their RNA samples were used for high-throughput sequencing purposes. Libraries were sequenced on the Illumina HiSeq2000 NGS platform.

2015-11-01 | E-GEOD-71613 | biostudies-arrayexpress

Microarray gene expression profiling of cardiac genes at the onset of heart failure

Project description:Atherosclerosis and pressure overload are major risk factors for the development of heart failure in patients. Cardiac hypertrophy often precedes the development of heart failure. However, underlying mechanisms are incompletely understood. To investigate pathomechanisms underlying the transition from cardiac hypertrophy to heart failure we used experimental models of atherosclerosis- and pressure overload-induced cardiac hypertrophy and failure, i.e. apolipoprotein E (apoE)-deficient mice, which develop heart failure at an age of 18 months, and non-transgenic C57BL/6J (B6) mice with heart failure triggered by 6 months of pressure overload induced by abdominal aortic constriction (AAC). The development of heart failure was monitored by echocardiography, invasive hemodynamics and histology. The microarray gene expression study of cardiac genes was performed with heart tissue from failing hearts relative to hypertrophic and healthy heart tissue, respectively. The microarray study revealed that the onset of heart failure was accompanied by a strong up-regulation of cardiac lipid metabolism genes involved in fat synthesis, storage and oxidation. Microarray gene expression profiling was performed with heart tissue isolated from (i) 18 month-old apoE-deficient mice relative to age-matched non-transgenic C57BL/6J (B6) mice, (ii) 6 month-old apoE-deficient mice with 2 months of chronic pressure overload induced by abdominal aortic constriction (AAC) relative to sham-operated apoE-deficient mice and nontransgenic B6 mice, (iii) 10 month-old B6 mice with 6 months of AAC relative to sham-operated B6 mice, and (iv) 5 month-old B6 mice with 1 month of AAC relative to age-matched B6 mice.

2010-12-03 | E-GEOD-25765 | biostudies-arrayexpress

Cellular landscapes of non-diseased human cardiac valves from end-stage heart failure-explanted heart

Project description:Exploring the mechanisms of valvular heart disease (VHD) at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of non-diseased human cardiac valve leaflets remains unclear. The cellular landscapes of non-diseased human cardiac valve leaflets (five aortic valves, five pulmonary valves, five tricuspid valves, and three mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing (scRNA-seq)

2022-09-13 | GSE213128 | GEO

lncExACT1 and DCHS2 Regulate Physiological and Pathological Cardiac Growth

Project description:The heart grows in response to pathological and physiological stimuli, while the former often precedes cardiomyocyte loss and heart failure, the latter paradoxically protects the heart and enhances cardiomyogenesis. Long noncoding RNAs (lncRNAs) are important in cardiac development and disease, less is known about their roles in physiological hypertrophy or cardiomyogenesis. The purpose of this study was to compare transcriptome profilings in exercise-induced physiological cardiac growth and stress-induced pathological cardiac growth. We identified a set of lncRNAs called long noncoding exercise associated cardiac transcripts (lncExACT). One of them, lncExACT1, whose cardiac expression was downregulated after exercise but upregulated after transverse aortic constriction. Inhibition of lncExACT1 induced physiolgoical cardiac growth while overexpression of lncExACT1 induced pathological hypertrophy and heart failure.

2022-10-18 | GSE186081 | GEO

Transcription profiling of spontaneously hypertensive heart failure rats (SHHF) and a reference strain to identify heart failure susceptibility genes

Project description:We aimed to identify gene variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure rats (SHHF) and reference strains. We combined linkage analyses with genome-wide expression profiling .

2008-09-01 | E-TABM-418 | biostudies-arrayexpress

RNA-Sequencing shows novel transcriptomic signatures in failing and non-failing human heart

2015-11-01 | GSE71613 | GEO