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@ARTICLE{Mller:141725,
      author       = {O. J. Müller and M. B. Heckmann and L. Ding and K. Rapti
                      and A. Y. Rangrez and T. Gerken and N. Christiansen and U.
                      E. E. Rennefahrt and H. Witt and S. G. Maldonado and P.
                      Ternes and D. M. Schwab and T. Ruf and S. Hille and A. Remes
                      and A. Jungmann and T. M. Weis and J. Kreußer and H.-J.
                      Gröne$^*$ and J. Backs and P. Schatz and H. A. Katus and N.
                      Frey},
      title        = {{C}omprehensive plasma and tissue profiling reveals
                      systemic metabolic alterations in cardiac hypertrophy and
                      failure.},
      journal      = {Cardiovascular research},
      volume       = {115},
      number       = {8},
      issn         = {1755-3245},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2018-01994},
      pages        = {1296-1305},
      year         = {2019},
      abstract     = {Heart failure is characterized by structural and metabolic
                      cardiac remodelling. The aim of the present study is to
                      expand our understanding of the complex metabolic
                      alterations in the transition from pathological hypertrophy
                      to heart failure and exploit the results from a
                      translational perspective.Mice were subjected to transverse
                      aortic constriction (TAC) or sham surgery and sacrificed 2,
                      4, or 6 weeks after the procedure. Samples from plasma,
                      liver, skeletal muscle, and heart were collected and
                      analysed using metabolomics. Cardiac samples were also
                      analysed by transcriptional profiling. Progressive
                      alterations of key cardiac metabolic pathways and gene
                      expression patterns indicated impaired mitochondrial
                      function and a metabolic switch during transition to heart
                      failure. Similar to the heart, liver and skeletal muscle
                      revealed significant metabolic alterations such as depletion
                      of essential fatty acids and glycerolipids in late stages of
                      heart failure. Circulating metabolites, particularly fatty
                      acids, reflected cardiac metabolic defects and deteriorating
                      heart function. For example, inverse correlation was found
                      between plasma and the heart levels of triacylglycerol
                      (C18:1, C18:2, C18:3), and sphingomyelin (d18:1, C23:0)
                      already at an early stage of heart failure. Interestingly,
                      combining metabolic and transcriptional data from cardiac
                      tissue revealed that decreased carnitine shuttling and
                      transportation preceded mitochondrial dysfunction. We, thus,
                      studied the therapeutic potential of OCTN2 (Organic
                      Cation/Carnitine Transporter 2), an important factor for
                      carnitine transportation. Cardiac overexpression of OCTN2
                      using an adeno-associated viral (AAV) vector significantly
                      improved ejection fraction and reduced interstitial fibrosis
                      in mice subjected to TAC.Comprehensive plasma and tissue
                      profiling reveals systemic metabolic alterations in heart
                      failure, which can be used for identification of novel
                      biomarkers and potential therapeutic targets.},
      cin          = {G130},
      ddc          = {610},
      cid          = {I:(DE-He78)G130-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30418544},
      doi          = {10.1093/cvr/cvy274},
      url          = {https://inrepo02.dkfz.de/record/141725},
}