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Dichloroacetate prevents restenosis in preclinical animal models of vessel injury

Author

Listed:
  • Tobias Deuse

    (TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Surgery, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany)

  • Xiaoqin Hua

    (TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Dong Wang

    (TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Lars Maegdefessel

    (Atherosclerosis Research Unit, Karolinska Institute, CMM L8:03, 17176 Stockholm, Sweden)

  • Joerg Heeren

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Ludger Scheja

    (University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Juan P. Bolaños

    (Institute of Functional Biology and Genomics, University of Salamanca-CSIC, Zacarias Gonzalez 2, 37007 Salamanca, Spain)

  • Aleksandar Rakovic

    (Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, 23562 Lübeck, Germany)

  • Joshua M. Spin

    (Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Mandy Stubbendorff

    (TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Fumiaki Ikeno

    (Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Florian Länger

    (Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany)

  • Tanja Zeller

    (Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany)

  • Leonie Schulte-Uentrop

    (Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Andrea Stoehr

    (Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Ryo Itagaki

    (TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Francois Haddad

    (Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Thomas Eschenhagen

    (Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Stefan Blankenberg

    (Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany)

  • Rainer Kiefmann

    (Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany)

  • Hermann Reichenspurner

    (Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Surgery, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany)

  • Joachim Velden

    (Institute of Pathology, University Hospital Erlangen, Krankenhausstraße 8-10, 91054 Erlangen, Germany)

  • Christine Klein

    (Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, 23562 Lübeck, Germany)

  • Alan Yeung

    (Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Robert C. Robbins

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Philip S. Tsao

    (Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
    Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue)

  • Sonja Schrepfer

    (TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
    Cardiovascular Surgery, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
    Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

Abstract

During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases.

Suggested Citation

  • Tobias Deuse & Xiaoqin Hua & Dong Wang & Lars Maegdefessel & Joerg Heeren & Ludger Scheja & Juan P. Bolaños & Aleksandar Rakovic & Joshua M. Spin & Mandy Stubbendorff & Fumiaki Ikeno & Florian Länger , 2014. "Dichloroacetate prevents restenosis in preclinical animal models of vessel injury," Nature, Nature, vol. 509(7502), pages 641-644, May.
    • Handle: RePEc:nat:nature:v:509:y:2014:i:7502:d:10.1038_nature13232
    DOI: 10.1038/nature13232
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