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nature portfolio permissions reprints privacy policy advertising nature glucose-6-phosphate dehydrogenase activity cyclic amp-mediated upregulation social media glucose-6-phosphate dehydrogenase gene glucose-6-phosphate dehydrogenase g6pd-deficient endothelial cells methylenetetrahydrofolate reductase-deficient mice angiotensin ii-dependent pathway article initially published aldosterone-induced inflammation aldosterone synthase-transgenic mice suppresses vascular angiotensin author correspondence modulates vascular function limiting oxidant stress springerlink instant access permissions mediated g6pd transcription impaired vascular reactivity high-salt diet camp-mediated repression increased oxidant stress g6pd-deficient phenotype aldosterone-induced vasculopathy endothelial cell lines personal data aortic endothelial cells restoring g6pd activity european economic area large artery compliance privacy aldosterone-treated cells vascular gene transfer programmed cell death data protection data interpretation impair endothelial function vascular response increasing g6pdh expression issue learn harvard medical school downstream transcription factors explore content subscription content /angiotensin ii conversion

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         description:Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). Here we show that aldosterone (10−9–;10−7 mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO• levels—similar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP−response element modulator (CREM) to inhibit cyclic AMP−response element binding protein (CREB)-mediated G6PD transcription. In vivo, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity. These effects were abrogated by spironolactone or vascular gene transfer of G6pd. These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6PD activity.
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      description:Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). Here we show that aldosterone (10−9–;10−7 mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO• levels—similar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP−response element modulator (CREM) to inhibit cyclic AMP−response element binding protein (CREB)-mediated G6PD transcription. In vivo, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity. These effects were abrogated by spironolactone or vascular gene transfer of G6pd. These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6PD activity.
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      affiliation:
            name:Whitaker Cardiovascular Institute
            address:
               name:Whitaker Cardiovascular Institute
               type:PostalAddress
            type:Organization
            name:Boston University School of Medicine
            address:
               name:Boston University School of Medicine, Boston, USA
               type:PostalAddress
            type:Organization
      name:Ronglih Liao
      affiliation:
            name:Whitaker Cardiovascular Institute
            address:
               name:Whitaker Cardiovascular Institute
               type:PostalAddress
            type:Organization
            name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
            address:
               name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
               type:PostalAddress
            type:Organization
            name:Boston University School of Medicine
            address:
               name:Boston University School of Medicine, Boston, USA
               type:PostalAddress
            type:Organization
      name:Diane E Handy
      affiliation:
            name:Whitaker Cardiovascular Institute
            address:
               name:Whitaker Cardiovascular Institute
               type:PostalAddress
            type:Organization
            name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
            address:
               name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
               type:PostalAddress
            type:Organization
            name:Boston University School of Medicine
            address:
               name:Boston University School of Medicine, Boston, USA
               type:PostalAddress
            type:Organization
      name:Robert C Stanton
      affiliation:
            name:Renal Section, Joslin Diabetes Center, 1 Joslin Place, Harvard Medical School
            address:
               name:Renal Section, Joslin Diabetes Center, 1 Joslin Place, Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
      name:Bertram Pitt
      affiliation:
            name:University of Michigan School of Medicine, Taubman Medical Center
            address:
               name:Division of Cardiology, University of Michigan School of Medicine, Taubman Medical Center, Ann Arbor, USA
               type:PostalAddress
            type:Organization
      name:Joseph Loscalzo
      affiliation:
            name:Whitaker Cardiovascular Institute
            address:
               name:Whitaker Cardiovascular Institute
               type:PostalAddress
            type:Organization
            name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
            address:
               name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
               type:PostalAddress
            type:Organization
            name:Boston University School of Medicine
            address:
               name:Boston University School of Medicine, Boston, USA
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Whitaker Cardiovascular Institute
      name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
      name:Boston University School of Medicine, Boston, USA
      name:Whitaker Cardiovascular Institute
      name:Boston University School of Medicine, Boston, USA
      name:Whitaker Cardiovascular Institute
      name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
      name:Boston University School of Medicine, Boston, USA
      name:Whitaker Cardiovascular Institute
      name:Boston University School of Medicine, Boston, USA
      name:Whitaker Cardiovascular Institute
      name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
      name:Boston University School of Medicine, Boston, USA
      name:Whitaker Cardiovascular Institute
      name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
      name:Boston University School of Medicine, Boston, USA
      name:Renal Section, Joslin Diabetes Center, 1 Joslin Place, Harvard Medical School, Boston, USA
      name:Division of Cardiology, University of Michigan School of Medicine, Taubman Medical Center, Ann Arbor, USA
      name:Whitaker Cardiovascular Institute
      name:Present address: Cardiovascular Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,
      name:Boston University School of Medicine, Boston, USA
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