Transcription profiling of mouse isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Cristi Lara Galindo
PROVIDER: E-GEOD-18801 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Cardiac hypertrophy consists in the enlargement of cardiomyocytes and alteration of the extracellular matrix organization in response to physiological or pathological stress. In pathological hypertrophy ocuurs myocardial damage, loss of cardiomyocytes, fibrosis, inflammation, sarcomere disorganization and metabolic impairment, leading to cardiac dysfunction.The rodent model treated with isoproterenol induces cardiac hypertrophy due the constant activation of β-adrenergic receptors. We conducted a quantitative label-free proteomic analysis of cardiomyocytes isolated from hearts of mice treated or not with isoproterenol to better understand the molecular bases of cellular response due to isoproterenol-induced injury.
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Project description:Genome-wide gene expression analysis of new cardiomyocytes (CMs) derived from resident c-kitpos endogenous cardiac stem cells (eCSCs) after myocardial injury by Isoproterenol (ISO) in mice. These data show that of new CMs derived from resident c-kitpos eCSCs have a gene expression profile that closely resembles the specific gene expression of adult cardiomyocytes. This result supports a role of c-kitpos eCSCs in the regeneration and repair of myocardial damage. To test the identity and the degree of differentiation of new cardiomyocytes (CMs) derived from resident c-kitpos endogenous cardiac stem cells (eCSCs) after myocardial injury by Isoproterenol (ISO) in mice. Global gene expression profiles by microarray was obtained in c-kitpos eCSCs, c-kitpos eCSC-derived YFPpos CMs and normal adult CMs. c-kitposCD45neg eCSCs were isolated from B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J mice and harvested at 4th passage (n=3). YFPpos cardiomyocytes were FACS sorted from left ventricle apex of Lentirius-c-kit/cre recombined B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J mice 28 days after ISO (N=3). Normal adult CMs were isolated from B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J mice (n=3).
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Project description:Myoglobin knockout mice (myo-/-) adapt to the loss of myoglobin by the activation of a variety of compensatory mechanisms on the structural and functional level. In order to analyze to what extent myo-/- mice would tolerate cardiac stress we used the model of chronic isoproterenol application to induce cardiac hypertrophy in myo-/- mice and wild type (WT) controls. After 14 d of isoproterenol infusion cardiac hypertrophy in WT and myo-/- mice reached a similar level. WT mice developed lung oedema and left ventricular dilatation indicating the development of heart failure. In contrast, myo-/- mice displayed conserved cardiac function and no signs of heart failure. Analysis of the cardiac gene expression profile using 40 k mouse oligonucleotide arrays showed that isoproterenol affected the expression of 180 genes in WT but only 92 genes of myo-/- hearts. Only 40 of these genes were regulated in WT and myo-/- hearts. Whereas in WT hearts a prononced induction of genes of the extracellular matrix occurred suggesting a higher level of remodelling, in myo-/- hearts genes of carbon metabolism and genes linked to inhibition of apoptosis and muscular repair were altered. Interestingly, a subset of genes which was altered in myo-/- mice already under basal conditions was differentially expressed in WT hearts under isoproterenol treatment. In summary, our data show, that the genetic background (WT, myo-/-) has a major impact on cardiac gene expression even in the context of an aggressive hypertrophy model such as chronic isoproterenol stimulation. Keywords: gene expression profiling of isoproterenol induced heart failure in WT and myo-/- mice We analysed the cardiac gene expression profiles in a total of 32 hearts subdivided into 4 groups (8 WT vehicle, 8 WT ISO, 8 myo-/- vehicle, 8 myo-/- ISO).
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Project description:Myoglobin knockout mice (myo-/-) adapt to the loss of myoglobin by the activation of a variety of compensatory mechanisms on the structural and functional level. In order to analyze to what extent myo-/- mice would tolerate cardiac stress we used the model of chronic isoproterenol application to induce cardiac hypertrophy in myo-/- mice and wild type (WT) controls. After 14 d of isoproterenol infusion cardiac hypertrophy in WT and myo-/- mice reached a similar level. WT mice developed lung oedema and left ventricular dilatation indicating the development of heart failure. In contrast, myo-/- mice displayed conserved cardiac function and no signs of heart failure. Analysis of the cardiac gene expression profile using 40 k mouse oligonucleotide arrays showed that isoproterenol affected the expression of 180 genes in WT but only 92 genes of myo-/- hearts. Only 40 of these genes were regulated in WT and myo-/- hearts. Whereas in WT hearts a prononced induction of genes of the extracellular matrix occurred suggesting a higher level of remodelling, in myo-/- hearts genes of carbon metabolism and genes linked to inhibition of apoptosis and muscular repair were altered. Interestingly, a subset of genes which was altered in myo-/- mice already under basal conditions was differentially expressed in WT hearts under isoproterenol treatment. In summary, our data show, that the genetic background (WT, myo-/-) has a major impact on cardiac gene expression even in the context of an aggressive hypertrophy model such as chronic isoproterenol stimulation. Keywords: gene expression profiling of isoproterenol induced heart failure in WT and myo-/- mice We analysed the cardiac gene expression profiles in a total of 32 hearts subdivided into 4 groups (8 WT vehicle, 8 WT ISO, 8 myo-/- vehicle, 8 myo-/- ISO).
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Project description:Cysteine oxidative modification of cellular proteins is crucial for many aspects of cardiac hypertrophy development. However, integrated dissection of multiple types of cysteine oxidation proteome in cardiac hypertrophy is currently missing. Here we developed a novel discovery platform encompassing a customized biotin switch-based quantitative proteomics pipeline and an advanced analytic workflow to comprehensively profile the landscape of cysteine oxidation in ISO-induced cardiac hypertrophy mouse model. Specifically, we identified a total of 3,717 proteins containing 6,837 oxidized cysteine sites by at least one of reversible cysteine oxidation, cysteine sulfinylation (CysSO2H), and cysteine sulfonylation (CysSO3H). Analyzing the hypertrophy signatures that are reproducibly discovered from computational workflow highlighted a group of fatty acid beta-oxidation enzymes with a continual decreased temporal pattern and a significant decreased abundance in reversible oxidation with no temporal or abundance change in total cysteine, revealing the oxidative regulatory map of fatty acid metabolism in cardiac hypertrophy, which is featured by an overall reduced oxidative metabolism. Our cysteine oxidation platform depicts a dynamic and integrated landscape of the cysteine oxidative proteome, extracted molecular signature, and provided mechanistic insights in cardiac hypertrophy.
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Project description:Transcriptomes performed on left ventricular heart samples from mice of the hybrid mouse diversity panel, a set of over a hundred inbred strains of mice. In this project, the strains were challenged with Isoproterenol, a beta-adrenergic agonist to induce cardiac hypertrophy and failure. Results are useful for the analysis of heart-related traits in mice Mice were given three weeks of ISO @ 20ug/g/day for three weeks, then sacrificed. Left ventricles from these mice and matched controls were used for transcripome analysis.
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