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PROVIDER: PRJNA830755 | ENA |
REPOSITORIES: ENA
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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).
2010-05-31 | E-GEOD-16243 | biostudies-arrayexpress
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).
2010-05-31 | E-GEOD-16246 | biostudies-arrayexpress
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.
2018-08-29 | PXD010336 | Pride
Project description:Sirtuin3 (SIRT3) is well known as a conserved nicotinamide adenine dinucleotide+ (NAD+)-dependent deacetylase located in the mitochondria that may regulate oxidative stress, catabolism and ATP production. Accumulating evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis, myocardial fibrosis and even heart failure (HF) , through its deacetylation modifications. Thus, discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently needed. Herein, we identified a new small-molecule activator of SIRT3 (named 2-APQC) by the structure-based drug designing strategy. 2-APQC was shown to alleviate isoproterenol (ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat models. Importantly, in SIRT3 knockout mice, 2-APQC could not relieve HF, suggesting that 2-APQC is dependent on SIRT3 for its protective role. Mechanically, 2-APQC inhibited the mammalian target of rapamycin-p70 ribosomal protein S6 kinase (p70S6K), c-jun N-terminal kinase (JNK) and transforming growth factor-β (TGF-β)/mothers against decapentaplegic homolog 3 (Smad3) pathways to improve ISO-induced cardiac hypertrophy and myocardial fibrosis. Based upon RNA-seq analyses, we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1 (PYCR1) axis was closely assoiated with HF. By activating PYCR1, 2-APQC could enhance mitochondrial proline metabolism, inhibited ROS-p38MAPK pathway and thereby protecting against ISO-induced oxidative damage. Moreover, activation of SIRT3 by 2-APQC could facilitate AMPK-Parkin axis to inhibit ISO-induced necrosis. Together, our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis, which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.
2024-02-28 | GSE260489 | GEO
Project description:tRNA-derived fragments (tRFs) have served as new class of non-coding RNA and played important role in regulating cellular RNA processing and protein translation, which was also proved have function on the intergenerational effects of paternal disease. However, there was no study reported the influence of tRFs on myocardial hypertrophy. In the current study, we explore the hypothesis that tRFs in response to myocardial hypertrophy and contribute to intergenerational inheritance.We used isoproterenol induced myocardial hypertrophy rat model. Small RNA (< 40 nt) tanscriptome sequencing was used to select differential expressed tRFs. We over-expressed the highest foldchange tRFs on H9c2 cell to check its function in enlarging cardiocytes surface area. We also compared the tRFs expression pattern in F0 sperm and F1 offspring heart between myocardial hypertrophy (Hyp) and control group (Con), as well as evaluated the phynotype of myocardial hypertrophy in F1 offspring. ISO successfully induced a typical cardiac hypertrophy model in our study. Small RNA-seq revealed tRFs were extremely enriched (84%) in Hyp heart. Overexpression tRFs1 and tRFs2 would both enlarge the surface area of cardiac cell and increase hypertrophic markers (ANF, BNP, and β-MHC) expression. tRFs1, tRFs2, tRFs3 and tRFs4 were also significantly high expressed in Hyp F0 sperm and in Hyp F1 offspring heart, but no function of tRFs7, tRFs9 and tRFs10. Compared to Con F1 offspring, Hyp F1 offspring had high expression levels of β-MHC and ANP genes, and increased fibrosis levles and apoptotic cell in heart.We demonstrate that tRFs are involved in regulating the response of myocardial hypertrophy, it might serve as novel epigenetic factor and contribute to intergenerational inheritance of cardiac hypertrophy.
2017-11-04 | GSE106511 | GEO
Project description:Background: Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic effects of fatty acid binding protein 3 (FABP3), on transverse aortic constriction (TAC)-induced cardiac hypertrophy. Methods and Results: TAC or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARα, which prevented its degradation and synergistically modulated its transcriptional activity on Mlycd, Gck. Finally, treatment with the PPARα agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency.
2021-06-12 | GSE177041 | GEO
Project description:Purpose: To identify the differential TFIIB bindingl patterns during postnatal cardiac growth, pressure-induced cardiac hypertrophy and adult mouse hearts Methods: Hearts were extracted from 1-2day old C57 mice, from mice subjecetd to Transaortic coarctation or adult mice. The hearts were sent to Active Motif for TFIIB- ChIP-Seq. Results: In accordance with previosly published data (Sayed D, et. al. JBC, 2013 Jan 25;288(4):2546-58) with genome wide polII and H3K9ac status during cardiac hypertrophy (GSE50637), Denovo TFIIB recruitment was restricted to speclaized genes with cardiac hypertrophy. Hearts were extracted from 1-2day old C57 mice, from mice subjecetd to Transaortic coarctation or adult mice. The hearts were sent to Active Motif for TFIIB- ChIP-Seq.
2014-11-17 | E-GEOD-56813 | biostudies-arrayexpress
Project description:We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively.
2009-10-31 | GSE18801 | GEO