| Autor: |
Bengel P; Clinic for Cardiology & Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany., Elkenani M; Clinic for Cardiology & Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany., Beuthner BE; Clinic for Cardiology & Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany., Pietzner M; MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UK.; Computational Medicine, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., Mohamed BA; Clinic for Cardiology & Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany., Pollok-Kopp B; Department of Transfusion Medicine, University Medical Center Göttingen, 37075 Göttingen, Germany., Krätzner R; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany., Toischer K; Clinic for Cardiology & Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany., Puls M; Clinic for Cardiology & Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany., Fischer A; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany.; Department of Clinical Chemistry, University Medical Center Göttingen, 37075 Göttingen, Germany.; Division Vascular Signaling and Cancer, German Cancer Research Center, 69120 Heidelberg, Germany., Binder L; Department of Clinical Chemistry, University Medical Center Göttingen, 37075 Göttingen, Germany., Hasenfuß G; Clinic for Cardiology & Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany., Schnelle M; DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany.; Department of Clinical Chemistry, University Medical Center Göttingen, 37075 Göttingen, Germany. |
| Abstrakt: |
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. |
