Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA879919 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21545437.fastq.gz | Fastqsanger.gz | |||
| SRR21545438.fastq.gz | Fastqsanger.gz | |||
| SRR21545439.fastq.gz | Fastqsanger.gz | |||
| SRR21545440.fastq.gz | Fastqsanger.gz | |||
| SRR21545441.fastq.gz | Fastqsanger.gz |
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Project description:Trans-aortic constriction (TAC) is a widely used murine model to study pressure overload-induced cardiac hypertrophy and heart failure. Despite its high prevalence during aortic stenosis or chronic arterial hypertension, the global alterations in cardiac proteome and phospho-proteome dynamics following TAC remain incompletely characterised. Here, we present a comprehensive database of detailing the phospho-proteomic signature of the mouse heart one day and seven days after TAC. Utilising proteomic and phosphor-proteomic analyses, we identified and quantified thousands of proteins and phosphorylation sites, revealing hundreds of differential phosphorylation events that are significantly altered in the cardiac response to pressure overload. Our analysis highlights significant changes in pathways related to hypertrophic signalling, metabolic remodelling, contractile function, and the stress response. We also present proteomic data from the main cardiac cell types (endothelial cells, fibroblasts and cardiomyocytes) after TAC to reveal the cellular localization of the detected phosphoproteins. The dataset offers insights into temporal and site-specific phosphorylation events, facilitating the potential discovery of novel therapeutic targets and biomarkers. By making this resource publicly available, we aim to enable further exploration of the molecular basis of cardiac remodelling and advance translational research in heart failure.
2025-05-26 | PXD061784 | Pride
Project description:Background: BMPER, an orthologue of Drosophila melanogaster crossveinless-2, is a secreted factor that regulates BMP activity in endothelial cell precursors and during early cardiomyocyte differentiation. Although previously described in the heart, the role of Bmper in cardiac development and function remained unknown. Methods: BMPER deficient hearts were phenotyped histologically and functionally using echocardiography and Doppler analysis. Since BMPER -/- mice die perinatally, BMPER +/- mice were then challenged to pressure overload induced cardiac hypertrophy and hind limb ischemia to determine changes in angiogensis and regulation of cardiomyocyte size. Results: We identified for the first time the cardiac phenotype associated with BMPER haploinsufficiency. BMPER mRNA and protein are present in the heart during cardiac development through at least E14.5 but is lost by E18.5. BMPER +/- ventricles are thinner and less compact than sibling wild-type hearts. In the adult, BMPER +/- hearts present with decreased anterior and posterior wall thickness, decreased cardiomyocyte size, and an increase in cardiac vessel density. Despite these changes, BMPER +/- mice respond to pressure overload-induced cardiac hypertrophy challenge largely to the same extent as wild-type mice. Conclusion: BMPER appears to play a role in regulating both vessel density and cardiac development in vivo; however, BMPER haploinsufficiency does not result in marked effects on cardiac function or adaptation to pressure overload hypertrophy. Unpaired, two-condition experiment, wild-type vs BMPER+/- adult hearts. Biological replicates: 4 per condition.
2012-09-20 | E-GEOD-40983 | biostudies-arrayexpress
Project description:Aims: In humans, secretome of pericardial (PAT) and epicardial adipose tissue (EAT) contribute to establishment of heart failure (HF) with preserved ejection fraction (HFpEF) originating from pressure-overload due to metabolic disorder. We examined whether PAT affects also manifestation and progression of pressure-induced HF in the absence of metabolic burden in mice. Methods and results: Progressive remodelling was assessed in C57BL/6J males, aged 9 wks, randomly assigned to sham surgery or transverse aortic constriction (TAC) for 1 week (early pressure-overload), 8 (chronic pressure-overload), or 12 weeks (HFrEF) with or without concomitant PAT excision. PAT removal did not affect early (1 wk TAC), and chronic (8 wks) pressure-overload induced concentric remodelling. However, the initial PAT excision prevented TAC-induced expansion of pro-inflammatory macrophages during early pressure-overload and attenuated the persistent LV expression of pro-hypertrophic, pro-inflammatory and pro-fibrotic factors as well as the drastic LV dilation and progressive systolic dysfunction in the long-term and thereby protected against the transition to HFrEF. This protection was associated with significant reduction of microscar and perivascular fibrosis. The latter was, at least in part, attributed to reduced accumulation of pro-fibrotic CD206+ macrophages around the coronaries 12 wks post-surgery in the absence of PAT compared to mice with intact PAT. In addition, PAT bulk RNA sequencing revealed the initiation of an extracellular matrix deposition programme in the PAT early upon TAC surgery, which might trigger fibrotic responses in the underlying myocardium. Indeed, isolated naive adult cardiac fibroblasts exposed to PAT lysate from 12 wks TAC mice increased collagen production and cell viability/proliferation. Conclusion: Our data suggest PAT to play divergent roles in the chronically pressure overloaded heart versus HFrEF - while widely not affecting concentric hypertrophy, PAT removal counteracts manifestation of HFrEF in mice, at least in part, by preventing excessive fibrotic and macrophage responses.
2024-12-06 | GSE283668 | GEO
Project description:A number of mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, protein synthesis, metabolism,autophagy, oxidative stress and inflammation. These mediators including nuclear transcription factor, microRNAs and long noncoding RNAs. However, the gene expression profiles signaling pathways in the pressure overload-induced cardiac hypertrophy remain unknown. All mice were randomly undertaken sham surgery or TAC for 2 weeks. Hearts were harvested 2 weeks following TAC and performed to further analysis.
2021-08-24 | GSE127954 | GEO
Project description:Background: Pathological cardiac overload triggers maladaptive myocardial remodeling that predisposes to the development of heart failure. The contribution of long non-coding RNAs (lncRNAs) to intercellular signaling during cardiac remodeling is largely unknown. Methods: We analyzed the expression of Gadlor 1 and Gadlor2 lncRNAs in mouse hearts, mouse cardiac cells, extracellular vesicles (EVs), human failing hearts as well as patient serum. Gadlor knock-out (KO) mice were generated and analyzed. The effect of Gadlor knock-out and Gadlor overexpression during cardiac pressure overload induced by transverse aortic constriction (TAC) was analyzed by echocardiography, histological analyses and RNA sequencing in isolated cardiac cells. Gadlor1/2 interaction partners were identified by RNA antisense purification coupled with mass-spectrometry (RAP-MS). Results: In the heart, the related lncRNAs Gadlor1 and 2 are mainly expressed in endothelial cells and to a lesser extent in fibroblasts. Gadlor1/2 are upregulated in failing mouse hearts as well as in the myocardium and in serum of heart failure patients. Interestingly, Gadlor1 and 2 are secreted from endothelial cells within EVs, which are taken up by cardiomyocytes. Gadlor-KO mice exerted reduced cardiomyocyte hypertrophy, diminished myocardial fibrosis and improved cardiac function, but paradoxically suffered from sudden death during prolonged overload. Gadlor overexpression, in turn, triggered hypertrophy, fibrosis and cardiac dysfunction. Mechanistically, Gadlor1 and Gadlor2 inhibit angiogenic gene expression in endothelial cells, while promoting the expression of pro-fibrotic genes in cardiac fibroblasts. In cardiomyocytes, Gadlor1/2 upregulate mitochondrial genes, but downregulate angiogenesis genes, while interacting with the transcriptional regulator Glyr1 and the calcium/calmodulin-dependent protein kinase type II (CaMKII), entailing cardiomyocyte hypertrophy and perturbed cardiomyocyte calcium dynamics. Conclusions: We describe that Gadlor1 and 2, two related, novel lncRNAs, are upregulated in cardiac pathological overload and are secreted from endothelial cells within EVs. Gadlor1/2 induce cardiac dysfunction, cardiomyocyte hypertrophy and myocardial fibrosis by exerting heterocellular effects on cardiac cellular gene-expression and by affecting calcium dynamics in cardiomyocytes, which take up the Gadlor1/2 by EV mediated transfer from endothelial cells. Targeted inhibition of Gadlor lncRNAs in endothelial cells or fibroblasts might serve as therapeutic strategy in the future.
2024-08-26 | GSE213612 | GEO
Project description:Pressure overload-induced cardiac hypertrophy was examined in IL-18 knockout and littermate control mice. Experiment Overall Design: 4 groups with RNA pooled from 5-6 per group. Role of IL-18 on gene expression in cardiac hypertrophy induced by pressure overload (transaortic constriction)
2008-06-13 | E-GEOD-5129 | biostudies-arrayexpress
Project description:Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. The role of cardiac long non-coding RNAs in cardiac hypertrophy and cardiomyopathy is not well understood. lincRNA-p21 was induced in mouse and human cardiomyopathy tissue. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 pathway. Mechanistically, lincRNA-p21 bound to the scaffold protein KAP1. lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulated pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. Importantly, GapmeR ASO depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21.
2024-06-11 | GSE262936 | GEO
Project description:Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. The role of cardiac long non-coding RNAs in cardiac hypertrophy and cardiomyopathy is not well understood. lincRNA-p21 was induced in mouse and human cardiomyopathy tissue. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 pathway. Mechanistically, lincRNA-p21 bound to the scaffold protein KAP1. lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulated pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. Importantly, GapmeR ASO depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21.
2024-06-11 | GSE262894 | GEO
Project description:Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. The role of cardiac long non-coding RNAs in cardiac hypertrophy and cardiomyopathy is not well understood. lincRNA-p21 was induced in mouse and human cardiomyopathy tissue. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 pathway. Mechanistically, lincRNA-p21 bound to the scaffold protein KAP1. lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulated pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. Importantly, GapmeR ASO depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21.
2024-06-11 | GSE262892 | GEO