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Questions {❓}

• Heusch G (2015) Mitochondria at the heart of cardiovascular protection: p66shc-friend or foe?

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         headline:Myocardial mitochondrial dysfunction in mice lacking adiponectin receptor 1
         description:Hypoadiponectinemia is an independent predictor of cardiovascular disease, impairs mitochondrial function in skeletal muscle, and has been linked to the pathogenesis of Type 2 diabetes. In models of Type 2 diabetes, myocardial mitochondrial function is impaired, which is improved by increasing serum adiponectin levels. We aimed to define the roles of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in adiponectin-evoked regulation of mitochondrial function in the heart. In isolated working hearts in mice lacking AdipoR1, myocardial oxygen consumption was increased without a concomitant increase in cardiac work, resulting in reduced cardiac efficiency. Activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes were reduced, accompanied by reduced OXPHOS protein levels, phosphorylation of AMP-activated protein kinase, sirtuin 1 activity, and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling. Decreased ATP/O ratios suggested myocardial mitochondrial uncoupling in AdipoR1-deficient mice, which was normalized by lowering increased mitochondrial 4-hydroxynonenal levels following treatment with the mitochondria-targeted antioxidant Mn (III) tetrakis (4-benzoic acid) porphyrin. Lack of AdipoR2 did not impair mitochondrial function and coupling in the heart. Thus, lack of AdipoR1 impairs myocardial mitochondrial function and coupling, suggesting that impaired AdipoR1 signaling may contribute to mitochondrial dysfunction and mitochondrial uncoupling in Type 2 diabetic hearts.
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      headline:Myocardial mitochondrial dysfunction in mice lacking adiponectin receptor 1
      description:Hypoadiponectinemia is an independent predictor of cardiovascular disease, impairs mitochondrial function in skeletal muscle, and has been linked to the pathogenesis of Type 2 diabetes. In models of Type 2 diabetes, myocardial mitochondrial function is impaired, which is improved by increasing serum adiponectin levels. We aimed to define the roles of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in adiponectin-evoked regulation of mitochondrial function in the heart. In isolated working hearts in mice lacking AdipoR1, myocardial oxygen consumption was increased without a concomitant increase in cardiac work, resulting in reduced cardiac efficiency. Activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes were reduced, accompanied by reduced OXPHOS protein levels, phosphorylation of AMP-activated protein kinase, sirtuin 1 activity, and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling. Decreased ATP/O ratios suggested myocardial mitochondrial uncoupling in AdipoR1-deficient mice, which was normalized by lowering increased mitochondrial 4-hydroxynonenal levels following treatment with the mitochondria-targeted antioxidant Mn (III) tetrakis (4-benzoic acid) porphyrin. Lack of AdipoR2 did not impair mitochondrial function and coupling in the heart. Thus, lack of AdipoR1 impairs myocardial mitochondrial function and coupling, suggesting that impaired AdipoR1 signaling may contribute to mitochondrial dysfunction and mitochondrial uncoupling in Type 2 diabetic hearts.
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            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Tilman Schnick
      affiliation:
            name:University of Freiburg
            address:
               name:Institute of Experimental and Clinical Pharmacology, University of Freiburg, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Adam R. Wende
      affiliation:
            name:University of Alabama at Birmingham
            address:
               name:Department of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, USA
               type:PostalAddress
            type:Organization
      name:Andrea Schrepper
      affiliation:
            name:Jena University Hospital
            address:
               name:Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany
               type:PostalAddress
            type:Organization
      name:Maria C. Cimolai
      affiliation:
            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Sophia Kersting
      affiliation:
            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Michael M. Hoffmann
      affiliation:
            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
            name:Freiburg University Hospital
            address:
               name:Institute for Clinical Chemistry and Laboratory Medicine, Freiburg University Hospital, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Judith Asal
      affiliation:
            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Moritz Osterholt
      affiliation:
            name:Jena University Hospital
            address:
               name:Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany
               type:PostalAddress
            type:Organization
      name:Katja E. Odening
      affiliation:
            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Torsten Doenst
      affiliation:
            name:Jena University Hospital
            address:
               name:Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany
               type:PostalAddress
            type:Organization
      name:Lutz Hein
      affiliation:
            name:University of Freiburg
            address:
               name:Institute of Experimental and Clinical Pharmacology, University of Freiburg, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:E. Dale Abel
      affiliation:
            name:Carver College of Medicine, University of Iowa
            address:
               name:Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, USA
               type:PostalAddress
            type:Organization
      name:Christoph Bode
      affiliation:
            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
      name:Heiko Bugger
      affiliation:
            name:Heart Center Freiburg University
            address:
               name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Institute of Experimental and Clinical Pharmacology, University of Freiburg, Freiburg, Germany
      name:Department of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, USA
      name:Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Institute for Clinical Chemistry and Laboratory Medicine, Freiburg University Hospital, Freiburg, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Department of Cardiothoracic Surgery, Jena University Hospital, Jena, Germany
      name:Institute of Experimental and Clinical Pharmacology, University of Freiburg, Freiburg, Germany
      name:Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, USA
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
      name:Division of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany
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