Dichloroacetate prevents restenosis in preclinical animal models of vessel injury

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, Tanja Zeller, Leonie Schulte-Uentrop, Andrea Stoehr, Ryo Itagaki, Francois Haddad, Thomas Eschenhagen, Stefan Blankenberg, Rainer Kiefmann, Hermann Reichenspurner, Joachim Velden, Christine Klein, Alan Yeung, Robert C. Robbins, Philip S. Tsao and Sonja Schrepfer ()
Additional contact information
Tobias Deuse: TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
Xiaoqin Hua: TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany
Dong Wang: TSI-laboratory, University Heart Center Hamburg, 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
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
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
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
Ryo Itagaki: TSI-laboratory, University Heart Center Hamburg, 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
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
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
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
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
Sonja Schrepfer: TSI-laboratory, University Heart Center Hamburg, Martinistraße 52, 20246 Hamburg, Germany

Nature, 2014, vol. 509, issue 7502, 641-644

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.

Date: 2014
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DOI: 10.1038/nature13232

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