Gene profiling of heart atria in PI3K and Mst1 mouse models
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE12420 | GEO | 2009/07/25
SECONDARY ACCESSION(S): PRJNA113117
REPOSITORIES: GEO
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Project description:We used microarrays to detail genome-wide gene expression underlying cardiac myocyte pathologies and identified candidate genes and specific pathways affecting cardiac myopathies Keywords: transgenics, cardiac disease analysis Mouse heart atria were dissected for RNA extraction and hybridisation on Affymetrix microarrays. We sought to profile gene expression from the transgenic mouse models for non-transgenics (Ntg), dnPI3K (dominant negative for phosphoinositide 3-kinase), Mst1 (mammalian sterile 20-like kinase 1) and dnPI3K-Mst1 (double mutant) mouse models with a combined background of C57BL/6/FVB/N inbred strains. Pathological insults on cardiac myocytes are investigated
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Project description:Cardiac hypertrophy can lead to heart failure, and is induced either by physiological stimuli eg postnatal development, chronic exrcise training or pathological stimuli eg pressure or volume overload. This data set looks at microRNA profiles in mouse models to examine whether phosphoinositide 3-kinase (p110 alpha isoform) activity is critical for the maintenance of cardiac function and long term survival in a seeting of heart failure (myocardial infarction). The significance and expected outcome are to recognise genes involved in models of heart failure and attempt to examine underlying regulator pathways involved in possible cardica maintenance in the PI3K mouse model. The matching mRNA gene expression profile (GSE7487) is examined to look for mRNA and microRNA interactions. miRNA expression correlates directly with cardiac function. PI3K regulon ameliorates cardiac stress. Keywords: microRNA profiling, regulatory pathway discovery, genotype comparison Ntg (non-transgenics), dnPI3K (cardiac-specific transgenic model with reduced PI3K activity) and caPI3K (transgenic mice with increased PI3K activity) mice at 3-4 months of age were used. Mice were then subjected to myocardial infarction (occlusion of the left anterior descending aorta) and sham (open heart surgery) for 8 weeks. Left ventricles were harvested. The resulting 6 experimental models were profiled accordingly. The assignment of the mouse models is as follows: caPI3K Sham, Ntg Sham, dnPI3K Sham, caPI3K MI (myocardial infarction), Ntg MI and dnPI3K MI with n = 4 in each group.
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2023-01-15 | PXD033078 | Pride
Project description:Dysregulation of ERalpha has been linked with increased metabolic and cardiovascular disease risk. Uncovering the impact of ERα deficiency in specific tissues has implications for understanding the role of ERα in normal physiology and disease, the increased disease risk in postmenopausal women, and the design of tissue-specific ERα-based therapies for a range of pathologies including cardiac disease and cancer. Cardiac myocyte-specific ER knockout mice (ERalphaHKO) were generated to assess the role of ERα in the heart. Female ERHKO mice displayed a mild cardiac phenotype, but unexpectedly, the most striking phenotype was obesity in female ERHKO but not male ERHKO mice. We identified mild cardiac dysfunction, metabolic and lipid dysregulation in hearts of female ERHKO mice. We also show that extracellular vesicles (EVs) collected from the perfusate from Langendorff-isolated hearts from female ERHKO mice have a distinct proteome compared to male ERHKO; enriched for functions associated with muscle, metabolic and fatty acid dysregulation.
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Project description:We characterized single-cell transcriptional profiles of heart ventricles of C57BL/6J female and male mice subjected to a chronic stress, two weeks of continuous administration of Angiotensin II. The cell preparation we sequenced consisted of metabolically active, nucleated non-myocyte cells which were depleted of endothelial cells, mixed with nuclei isolated from cardiomyocytes. The goal of this experiment included characterizing cellular diversity in stressed and unstressed hearts, uncovering potential drivers of cardiac fibrosis and hypertrophy, and quantifying sexual dimorphism in cardiac gene expression.
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