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@ARTICLE{Bengel:212430,
      author       = {P. Bengel and M. Elkenani and B. E. Beuthner and M.
                      Pietzner and B. A. Mohamed and B. Pollok-Kopp and R.
                      Krätzner and K. Toischer and M. Puls and A. Fischer$^*$ and
                      L. Binder and G. Hasenfuß and M. Schnelle},
      title        = {{M}etabolomic {P}rofiling in {P}atients with {D}ifferent
                      {H}emodynamic {S}ubtypes of {S}evere {A}ortic {V}alve
                      {S}tenosis.},
      journal      = {Biomolecules},
      volume       = {13},
      number       = {1},
      issn         = {2218-273X},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-00149},
      pages        = {95},
      year         = {2023},
      abstract     = {Severe aortic stenosis (AS) is a common pathological
                      condition in an ageing population imposing significant
                      morbidity and mortality. Based on distinct hemodynamic
                      features, i.e., ejection fraction (EF), transvalvular
                      gradient and stroke volume, four different AS subtypes can
                      be distinguished: (i) normal EF and high gradient, (ii)
                      reduced EF and high gradient, (iii) reduced EF and low
                      gradient, and (iv) normal EF and low gradient. These
                      subtypes differ with respect to pathophysiological
                      mechanisms, cardiac remodeling, and prognosis. However,
                      little is known about metabolic changes in these different
                      hemodynamic conditions of AS. Thus, we carried out
                      metabolomic analyses in serum samples of 40 AS patients (n =
                      10 per subtype) and 10 healthy blood donors (controls) using
                      ultrahigh-performance liquid chromatography-tandem mass
                      spectroscopy. A total of 1293 biochemicals could be
                      identified. Principal component analysis revealed different
                      metabolic profiles in all of the subgroups of AS (All-AS)
                      vs. controls. Out of the determined biochemicals, $48\%$ (n
                      = 620) were altered in All-AS vs. controls (p < 0.05). In
                      this regard, levels of various acylcarnitines (e.g.,
                      myristoylcarnitine, fold-change 1.85, p < 0.05), ketone
                      bodies (e.g., 3-hydroxybutyrate, fold-change 11.14, p <
                      0.05) as well as sugar metabolites (e.g., glucose,
                      fold-change 1.22, p < 0.05) were predominantly increased,
                      whereas amino acids (e.g., leucine, fold-change 0.8, p <
                      0.05) were mainly reduced in All-AS. Interestingly, these
                      changes appeared to be consistent amongst all AS subtypes.
                      Distinct differences between AS subtypes were found for
                      metabolites belonging to hemoglobin metabolism,
                      diacylglycerols, and dihydrosphingomyelins. These findings
                      indicate that relevant changes in substrate utilization
                      appear to be consistent for different hemodynamic subtypes
                      of AS and may therefore reflect common mechanisms during
                      AS-induced heart failure. Additionally, distinct metabolites
                      could be identified to significantly differ between certain
                      AS subtypes. Future studies need to define their
                      pathophysiological implications.},
      keywords     = {heart failure (Other) / hemodynamic subgroups (Other) /
                      metabolic remodeling (Other) / metabolomics (Other) / severe
                      aortic valve stenosis (Other)},
      cin          = {A270},
      ddc          = {570},
      cid          = {I:(DE-He78)A270-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36671480},
      pmc          = {pmc:PMC9855798},
      doi          = {10.3390/biom13010095},
      url          = {https://inrepo02.dkfz.de/record/212430},
}