Metabolomics in the cardiovascular system

Research focus

The working group focuses on the study of the metabolome in relation to cardiovascular disease and its metabolic risk factors. The "metabolome" encompasses the concept of the totality of all small metabolites, so-called "metabolites", in blood, urine or a tissue. Analysis of the metabolome allows metabolic pathways to be analyzed in their entirety in order to uncover pathomechanisms and biomarkers and to generate new hypotheses.

A particular focus of the research group is the study of metabolites circulating in the blood, which originate from the metabolism of the intestinal flora. The bacterial intestinal flora has a close relationship with the host organism and is involved in many physiological processes. Disruption of this symbiosis has been associated with various metabolic and cardiovascular diseases. Circulating metabolites play a crucial role as mediators in the crosstalk between intestinal flora and host organism.

Principal Investigator

Dr. Dr. med. Ben Arpad Kappel

Research team members

Maren Gesper (M.Sc.)

Dr. med. Andreas Pütz

Alena Nonnast

M.D. students

Victoria Michaklczyk (Cand. med.)

Maximilian Pulwey (Cand. med.)

  • Characterization of cardiac energetics in heart failure in type 2 diabetes mellitus.
    The incidence of heart failure is higher in individuals with type 2 diabetes mellitus, which also leads to more severe disease courses. However, the precise mechanisms by which diabetes affects the heart remain poorly understood. There is a possibility that changes in cardiac energy metabolism may contribute to a poorer prognosis in patients with heart failure. The objective of this research project is to characterize cardiac metabolism in patients with chronic heart failure, both with and without diabetes, through the use of metabolomic analysis. We aim to elucidate how diabetes alters substrate utilization in the heart (e.g., the shift from fatty acid metabolism to glucose metabolism), which could provide the basis for novel therapeutic approaches for the management of chronic heart failure.

    Funded by the Else Kröner-Fresenius-Stiftung.

  • The impact of gut-derived metabolites on the cardiovascular system
    The human gut microbiota is known to produce a diverse array of metabolites that are absorbed by the host and possess biological activity. Some of these metabolites have been implicated in the pathogenesis of cardiovascular disease. However, the biological functions and roles of many other gut microbiota-derived metabolites in the cardiovascular system remain poorly understood. Several research projects of our group aim to address this knowledge gap.

    This research is supported by the German Heart Research Foundation and the START program of RWTH Aachen University.

For a complete reference list please see PubMed* Link

Selected publications:

  • Effect of Empagliflozin on the Metabolic Signature of Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease.
    Kappel BA, Lehrke M, Schütt K, Artati A, Adamski J, Lebherz C, Marx N.
    Circulation. 2017. doi:10.1161/CIRCULATIONAHA.117.02916
  • Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment.
    Kappel BA, De Angelis L, Heiser M, Ballanti M, Stoehr R, Goettsch C, Mavilio M, Artati A, Paoluzi OA, Adamski J, Mingrone G, Staels S, Burcelin R, Monteleone G, Menghini R, Marx N, Federici M.
    Mol Metab. 2020. doi:10.1016/j.molmet.2020.100976
  • Antibiotic-induced gut microbiota depletion exacerbates host hypercholesterolemia.
    Kappel BA, De Angelis L, Puetz A, Ballanti M, Menghini R, Marx N, Federici M.
    Pharmacol Res. 2022. doi: 10.1016/j.phrs.2022.106570
  • Human and mouse non-targeted metabolomics identify 1,5-anhydroglucitol as SGLT2-dependent glycemic marker.
    Kappel BA, Moellmann J, Thiele K, Rau M, Artati A, Adamski J, Ghesquiere B, Schuett K, Romeo F, Stoehr R, Marx N, Federici M, Lehrke M.
    Clin Transl Med. 2021. doi:10.1002/ctm2.470
  • Non-targeted metabolomics identify polyamine metabolite acisoga as novel biomarker for reduced left ventricular function.
    Puetz A, Artati A, Adamski J, Schuett S, Romeo F, Stoehr R, Marx N, Federici M, Lehrke M, Kappel BA.
    ESC Heart Fail. 2021. doi:10.1002/ehf2.13713
  • Gut-derived metabolite indole-3-propionic acid modulates mitochondrial function in cardiomyocytes and alters cardiac function.
    Gesper M, Nonnast AB, Kumowski N, Stöhr R, Schütt K, Marx N, Kappel BA.
    Front Med. 2021. doi:10.3389/fmed.2021.648259
  • 2-hydroxycaproate predicts cardiovascular mortality in patients with atherosclerotic disease.
    Cardellini M, Ballanti M, Davato F, Cardolini I, Guglielmi V, Rizza S, Pecchioli C, Viviana Casagrande V, Mavilio M, Porzio O, Legramante JM, Ippoliti A, Farcomeni A, Sbraccia P, Menghini R, Dumas MED, Kappel BA*, Federici M*
    Atherosclerosis. 2018. doi:10.1016/j.atherosclerosis.2018.06.014.
  • A role for Timp3 in microbiota-driven hepatic steatosis and metabolic dysfunction.
    Mavilio M, Marchetti V, Fabrizi M, Stöhr R, Marino A, Casagrande V, Fiorentino L, Cardelli M, Kappel B, Monteleone I, Garret C, Mauriello A, Monteleone G, Farcomeni A, Burcelin R, Menghini R, Federici M.
    Cell Rep. 2016. 16(3) 731-743. doi:10.1016/j.celrep.2016.06.027
  • TIMP3 interplays with apelin to regulate cardiovascular metabolism in hypercholesterolemic mice.
    Stöhr R*, Kappel B*, Carnevale D*, Cavalera M, Mavilio M, Arisi I, Fardella V, Cifelli G, Casagrande V, Rizza S, Cattaneo A, Mauriello A, Menghini R, Lembo G, Federici M
    Mol. Metab. 2015. doi:10.1016/j.molmet.2015.07.007.
  • Posttranslational modulation of FoxO1 contributes to cardiac remodeling in post-ischemic heart failure.
    Kappel B*, Stöhr R*, De Angelis L, Mavilio M, Menghini R, Federici M.
    Atherosclerosis. 2016. doi:10.1016/j.atherosclerosis.2016.04.001
  • Else Kröner-Fresenius-Stiftung
  • German Heart Foundation
  • German Heart Research Foundation  
  • START-Programm der RWTH Aachen