Metabolomic Profiling in Patients with Different Hemodynamic Subtypes of Severe Aortic Valve Stenosis
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Metabolomic Profiling in Patients with Different Hemodynamic Subtypes of Severe Aortic Valve Stenosis
Bengel, P.; Elkenani, M.; Beuthner, B. E.; Pietzner, M.; Mohamed, B. A.; Pollok-Kopp, B. & Krätzner, R. et al. (2023)
Biomolecules, 13(1) pp. 95. DOI: https://doi.org/10.3390/biom13010095
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Details
- Authors
- Bengel, Philipp; Elkenani, Manar; Beuthner, Bo E.; Pietzner, Maik; Mohamed, Belal A.; Pollok-Kopp, Beatrix; Krätzner, Ralph; Toischer, Karl; Puls, Miriam; Fischer, Andreas; Schnelle, Moritz
- 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.
- Issue Date
- 2023
- Journal
- Biomolecules
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur
SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz - Working Group
- RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)
RG Hasenfuß (Transition zur Herzinsuffizienz)
RG Toischer (Kardiales Remodeling) - eISSN
- 2218-273X
- Language
- English
- Sponsor
- Open-Access-Publikationsfonds 2022