Transcriptional remodeling effects of the nuclear receptor NR4A2 in adult rat ventricular myocytes
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PROVIDER: PRJNA506897 | ENA |
REPOSITORIES: ENA
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Project description:Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early response gene activated in the heart under beta-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by NR4A2 expression in cardiomyocytes, and their impact on the physiological response of those cells to sustained beta-adrenergic stimulation. Treatment of adult rat ventricular myocytes (ARVMs) with isoproterenol induced a rapid (< 4 hours) but transient (< 24 hours) increase in NR4A2 expression levels that was accompanied by increased nuclear localization of the transcription factor. Adenovirus-mediated overexpression of NR4A2 modulated the expression of genes linked to adrenoceptor signaling, calcium signaling, cell growth and proliferation, and counteracted the increase in protein synthesis rate and cell surface area mediated by chronic isoproterenol stimulation. In consistence with those findings, NR4A2 overexpression also blocked the phosphorylative activation of ERK1/2, Akt, and of their downstream effector in protein synthesis p70S6K. Prominent among the transcriptional changes induced by NR4A2 was the > 7-fold up-regulation of the dual-specificity phosphatases DUSP2 and DUSP14, two known inhibitors of ERK1/2. Pre-treatment of NR4A2-overexpressing cardiomyocytes with the DUSPs inhibitor BCI prevented the inhibition of ERK1/2 and p70S6K following isoproterenol stimulation. In conclusion, our results suggest that NR4A2 acts as a novel negative feedback regulator of the beta-adrenergic receptor-mediated growth response in cardiomyocytes, and this at least partly through DUSP-mediated inhibition of ERK1/2 signaling.
2018-11-27 | GSE122911 | GEO
Project description:Ischemic cardiomyopathy (ICM) leads to congestive heart failure and can cause sudden cardiac death due to arrhythmia. Existing molecular knowledge base of ICM is rudimentary because of lack of specific attribution to cell type and function. This study was designed to investigate cell-specific molecular remodeling of ion channels, exchangers and pumps, which are signaling molecules (SM) involved in electrical, signaling and mechanical functions of the heart. Atrial and ventricular myocytes were isolated by laser-capture microdissection from left atrium and ventricle of healthy and ICM human hearts. SM and their splice variants altered by ICM in cardiomyocytes were identified by splice microarray and validated by RT-PCR. Molecular profiling of ICM-related changes showed that SM in atrial and ventricular myocytes remodel following their unique programs. ICM affected 63 genes in ventricular myocytes and 12 genes in atrial myocytes. Only few of the identified genes were previously linked to human cardiac disfunctions. In our experiments we used 3 healthy hearts rejected from transplantation procedure and explanted ICM hearts from three male patients. Tissue samples were dissected from left ventricle and left atrial appendages. Atrial and ventricular myocytes were laser-capture microdissected from serial 7-8-µm thick cryostat sections. Individual cellular total RNA samples were analyzed on custom-built Human Ion Channel Splice Arrays slides (ExonHit) manufactured on the Ion Channel Splice Array sv1.1 platform representing 287 human SM, including 248 alternatively spliced ones in total 1655 splicing events and supplemented with capabilities to recognize connexins and ryanodine receptors.
2010-05-14 | E-GEOD-17294 | biostudies-arrayexpress
Project description:Ischemic cardiomyopathy (ICM) leads to congestive heart failure and can cause sudden cardiac death due to arrhythmia. Existing molecular knowledge base of ICM is rudimentary because of lack of specific attribution to cell type and function. This study was designed to investigate cell-specific molecular remodeling of ion channels, exchangers and pumps, which are signaling molecules (SM) involved in electrical, signaling and mechanical functions of the heart. Atrial and ventricular myocytes were isolated by laser-capture microdissection from left atrium and ventricle of healthy and ICM human hearts. SM and their splice variants altered by ICM in cardiomyocytes were identified by splice microarray and validated by RT-PCR. Molecular profiling of ICM-related changes showed that SM in atrial and ventricular myocytes remodel following their unique programs. ICM affected 63 genes in ventricular myocytes and 12 genes in atrial myocytes. Only few of the identified genes were previously linked to human cardiac disfunctions.
2010-02-18 | GSE17294 | GEO
Project description:Neonatal rat ventricular myocytes cultured for 48 hours without stimulation, in the presence of twenty micromolar phenylephrine, or in the presence of one micromolar PAMH. Keywords = Rattus Keywords = Ventricular Myocytes Keywords = Cardiomyocytes Keywords = Hypertrophy Keywords = Phenylephrine Keywords = PAMH Keywords = 5-hydroxytryptamine Keywords = Pyridine Keywords: repeat sample
2004-03-02 | GSE925 | GEO
Project description:Title: Regulation of gene expression through mitogen-activated protein kinase cascades in cardiac myocytes.<br/> Description: The aim of this study is to identify the changes in gene expression induced in rat neonatal <br/> ventricular myocytes, a well-established cell culture model, by endothelin-1, <br/> a known hypertrophic agonist, and to determine which of the changes are <br/> mediated through the ERK cascade. This continues TKAC^Ys previous study of the <br/> effects of oxidative stress, which induces cardiac myocyte apoptosis.<br/>
2006-10-01 | E-MIMR-3 | biostudies-arrayexpress
Project description:Loss of KChIP2 during cardiac stress has been suggested to have a transcriptional impact on cardiac ion channels contributing to maladaptive electrical remodeling. Therefore, we tested the consequence of KChIP2 loss, in the absence of cardiac stress, by treating cultured neonatal rat ventricular myocytes with shRNA for KChIP2 and subsequently performed whole-transcriptome microarray analysis to identify gene changes.
2017-02-20 | GSE94623 | GEO
Project description:Loss of KChIP2 during cardiac stress has been suggested to have a transcriptional impact on cardiac ion channels through altered miRNA activity, contributing to maladaptive electrical remodeling. Therefore, we tested the consequence of KChIP2 loss, in the absence of cardiac stress, by treating cultured neonatal rat ventricular myocytes with siRNA for KChIP2 and subsequently performed miRNA microarray analysis to identify up-regulation of potential miRNA targets.
2017-02-20 | GSE75806 | GEO
Project description:Neonatal rat ventricular myocytes cultured for 48 hours without stimulation, in the presence of twenty micromolar phenylephrine, or in the presence of one micromolar PAMH.
2008-06-16 | E-GEOD-925 | biostudies-arrayexpress
Project description:Title: Regulation of gene expression through mitogen-activated protein kinase cascades in cardiac myocytes.<br/> Description: We aim to identify the changes in gene expression induced in rat <br/> neonatal ventricular myocytes, a well established cell culture model, <br/> by phenylepherine, a known hypertrophic agonist, and to determine which <br/> of the changes are mediated through the ERK cascade. In addition, we <br/> intend to extend the previous studies (EXP_TKAC_0102_01 and <br/> EXP_TKAC_1103_02) on endothelin-1 induced hypertrophy and the oxidative <br/> stress induced by H2O2 by using additional concentrations and timepoints.
2006-10-01 | E-MIMR-37 | biostudies-arrayexpress
Project description:Study of the effects of interleukin 1 beta on transcript expression in ventricular cardiac myocytes
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