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nurko, mice, cardiac, cardiomyocytes, article, cas, google, scholar, stimulation, heart, expression, isoproterenol, remodelling, significantly, cai, βadrenergic, compared, fig, cardiomyocyte, cells, receptor, calcineurin, observed, nuclear, hearts, assessed, data, failure, enhanced, role, gene, usa, nature, ventricular, cell, shown, function, chronic, pressure, hypertrophy, nrvms, protein, adverse, increased, tac, isolated, activity, activation, nra, performed,

Topics {✒️}

contributed reagents/materials/analysis tools/financially nature portfolio privacy policy enhanced open probability amphotericin-perforated patch-clamp technique author information authors lipid loading/foam-cell formation13 anti-rabbit-igg-hrp polymer advertising angiotensin-ii-induced pressure overload nature 415 nature 386 nature enhancing reverse na+/ca2+-exchange social media ca2+-calmodulin-activated phosphatase calcineurin6 cardiac ca2+-handling-related genes 0/ reprints isoproterenol-treated nur77-ko mice isoproterenol-treated nur77-ko cardiomyocytes calcium-regulated transcriptional pathways japan cardiomyocyte cross-sectional area isoproterenol-induced cardiac remodelling form pro-arrhythmic substrates30 tac-induced pressure overload bone marrow-specific deficiency β-myosin heavy chain 2d m-mode tracings loading control β-actin chronic angiotensin-ii infusion16 full size image cardiomyocyte β-adrenergic receptors nur77-ko mice exhibited cardiac excitation-contraction coupling β-adrenergic receptor activation β-adrenergic receptors occurs cardiac-specific nur77 knock calmodulin-dependent protein kinases ly-6chigh monocytes depend β-adrenergic agonist isoproterenol voltage-dependent calcium channels multi-tissue northern blots chronic β-adrenergic stimulation nur77-ko mice showed pro-inflammatory macrophage polarization10 regulate excitation-contraction coupling kolmogorov-smirnov normality test northern blot analysis nur77-ko ventricular tissue

Questions {❓}

• However, how do these data relate to the existing Nur77 data on cardiac remodelling?

Schema {🗺️}

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         headline:Orphan nuclear receptor Nur77 affects cardiomyocyte calcium homeostasis and adverse cardiac remodelling
         description:Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes and more cardiac fibrosis in Nur77-KO mice upon chronic isoproterenol stimulation. In line with the observed elevated [Ca2+]i, Ca2+-activated phosphatase calcineurin was more active in Nur77-KO mice compared to WT. In contrast, after cardiac pressure overload by aortic constriction, Nur77-KO mice exhibited attenuated remodelling compared to WT. Concluding, Nur77-deficiency results in significantly altered cardiac Ca2+ homeostasis and distinct remodelling outcome depending on the type of insult. Detailed knowledge on the role of Nur77 in maintaining cardiomyocyte Ca2+ homeostasis and the dual role Nur77 plays in cardiac remodelling will aid in developing personalized therapies against heart failure.
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      headline:Orphan nuclear receptor Nur77 affects cardiomyocyte calcium homeostasis and adverse cardiac remodelling
      description:Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes and more cardiac fibrosis in Nur77-KO mice upon chronic isoproterenol stimulation. In line with the observed elevated [Ca2+]i, Ca2+-activated phosphatase calcineurin was more active in Nur77-KO mice compared to WT. In contrast, after cardiac pressure overload by aortic constriction, Nur77-KO mice exhibited attenuated remodelling compared to WT. Concluding, Nur77-deficiency results in significantly altered cardiac Ca2+ homeostasis and distinct remodelling outcome depending on the type of insult. Detailed knowledge on the role of Nur77 in maintaining cardiomyocyte Ca2+ homeostasis and the dual role Nur77 plays in cardiac remodelling will aid in developing personalized therapies against heart failure.
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      name:Daniella Cakici
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:Maarten M. G. van den Hoogenhof
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:Farid Meggouh
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:Esther E. Creemers
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:Carol Ann Remme
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:Antonius Baartscheer
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:Robbert J. de Winter
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Cardiology, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:Carlie J. M. de Vries
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
      name:E. Karin Arkenbout
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Cardiology, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
            name:Tergooi Hospital
            address:
               name:Department of Cardiology, Tergooi Hospital, Blaricum, The Netherlands
               type:PostalAddress
            type:Organization
      name:Vivian de Waard
      affiliation:
            name:University of Amsterdam, The Netherlands
            address:
               name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
      name:Department of Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam, The Netherlands
      name:Division of Cardiology, Thoraxcenter, Erasmus Medical Center, University of Rotterdam, The Netherlands
      name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
      name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
      name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
      name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,
      name:Department of Cardiology, University of Amsterdam, The Netherlands,
      name:Department of Cardiology, Tergooi Hospital, Blaricum, The Netherlands
      name:Department of Medical Biochemistry, University of Amsterdam, The Netherlands,

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