% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Jabs:136031,
      author       = {M. Jabs$^*$ and A. J. Rose and L. H. Lehmann and J.
                      Taylor$^*$ and I. Moll$^*$ and T. Sijmonsma$^*$ and S. E.
                      Herberich$^*$ and S. W. Sauer and G. Poschet and G.
                      Federico$^*$ and C. Mogler and E.-M. Weis$^*$ and H.
                      Augustin$^*$ and M. Yan and N. Gretz and R. M. Schmid and R.
                      H. Adams and H.-J. Gröne and R. Hell and J. G. Okun and J.
                      Backs and P. P. Nawroth and S. Herzig and A. Fischer$^*$},
      title        = {{I}nhibition of {E}ndothelial {N}otch {S}ignaling {I}mpairs
                      {F}atty {A}cid {T}ransport and {L}eads to {M}etabolic and
                      {V}ascular {R}emodeling of the {A}dult {H}eart.},
      journal      = {Circulation},
      volume       = {137},
      number       = {24},
      issn         = {1524-4539},
      address      = {Philadelphia, Pa.},
      publisher    = {Lippincott, Williams $\&$ Wilkins},
      reportid     = {DKFZ-2018-00731},
      pages        = {2592 - 2608},
      year         = {2018},
      abstract     = {Nutrients are transported through endothelial cells before
                      being metabolized in muscle cells. However, little is known
                      about the regulation of endothelial transport processes.
                      Notch signaling is a critical regulator of metabolism and
                      angiogenesis during development. Here, we studied how
                      genetic and pharmacological manipulation of endothelial
                      Notch signaling in adult mice affects endothelial fatty acid
                      transport, cardiac angiogenesis, and heart
                      function.Endothelial-specific Notch inhibition was achieved
                      by conditional genetic inactivation of Rbp-jκ in adult mice
                      to analyze fatty acid metabolism and heart function.
                      Wild-type mice were treated with neutralizing antibodies
                      against the Notch ligand Delta-like 4. Fatty acid transport
                      was studied in cultured endothelial cells and transgenic
                      mice.Treatment of wild-type mice with Delta-like 4
                      neutralizing antibodies for 8 weeks impaired fractional
                      shortening and ejection fraction in the majority of mice.
                      Inhibition of Notch signaling specifically in the
                      endothelium of adult mice by genetic ablation of Rbp-jκ
                      caused heart hypertrophy and failure. Impaired heart
                      function was preceded by alterations in fatty acid
                      metabolism and an increase in cardiac blood vessel density.
                      Endothelial Notch signaling controlled the expression of
                      endothelial lipase, Angptl4, CD36, and Fabp4, which are all
                      needed for fatty acid transport across the vessel wall. In
                      endothelial-specific Rbp-jκ-mutant mice, lipase activity
                      and transendothelial transport of long-chain fatty acids to
                      muscle cells were impaired. In turn, lipids accumulated in
                      the plasma and liver. The attenuated supply of
                      cardiomyocytes with long-chain fatty acids was accompanied
                      by higher glucose uptake, increased concentration of
                      glycolysis intermediates, and mTOR-S6K signaling. Treatment
                      with the mTOR inhibitor rapamycin or displacing glucose as
                      cardiac substrate by feeding a ketogenic diet prolonged the
                      survival of endothelial-specific Rbp-jκ-deficient mice.This
                      study identifies Notch signaling as a novel regulator of
                      fatty acid transport across the endothelium and as an
                      essential repressor of angiogenesis in the adult heart. The
                      data imply that the endothelium controls cardiomyocyte
                      metabolism and function.},
      cin          = {A270 / G130 / A190},
      ddc          = {610},
      cid          = {I:(DE-He78)A270-20160331 / I:(DE-He78)G130-20160331 /
                      I:(DE-He78)A190-20160331},
      pnm          = {321 - Basic Concepts (POF3-321)},
      pid          = {G:(DE-HGF)POF3-321},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29353241},
      doi          = {10.1161/CIRCULATIONAHA.117.029733},
      url          = {https://inrepo02.dkfz.de/record/136031},
}