1. Energy metabolites as biomarkers in ischemic and dilated cardiomyopathy
- Author
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Benjamin Meder, Oguz Firat Tugrul, Michael P. Murphy, Ali Amr, Michael Wisdom, Stephan B. Felix, Jens Fielitz, Rouven Nietsch, Norbert Frey, Marcus Dörr, Uwe Völker, Elham Kayvanpour, Rewati Tappu, Karen S. Frese, Andreas Keller, Jan Haas, Torsten Dr. Niederdränk, Hugo A. Katus, Carsten Dietrich, Tanja Weis, Farbod Sedaghat-Hamedani, Thomas Krieg, Sedaghat-Hamedani, Farbod [0000-0002-3266-0527], Tappu, Rewati [0000-0003-0902-7114], Niederdränk, Torsten [0000-0002-3803-2679], Krieg, Thomas [0000-0002-5192-580X], Dörr, Marcus [0000-0001-7471-475X], Völker, Uwe [0000-0002-5689-3448], Keller, Andreas [0000-0002-5361-0895], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Epigenomics ,Male ,Metabolite ,Cardiomyopathy ,heart failure ,030204 cardiovascular system & hematology ,Pharmacology ,Epigenesis, Genetic ,lcsh:Chemistry ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,energy metabolism ,Glycolysis ,lcsh:QH301-705.5 ,Spectroscopy ,Principal Component Analysis ,Dilated cardiomyopathy ,General Medicine ,Middle Aged ,Computer Science Applications ,DNA methylation ,Female ,Adult ,Cardiomyopathy, Dilated ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Metabolomics ,medicine ,Humans ,Epigenetics ,Physical and Theoretical Chemistry ,Molecular Biology ,Aged ,business.industry ,Gene Expression Profiling ,Organic Chemistry ,multi-omics ,medicine.disease ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cardiovascular and Metabolic Diseases ,Heart failure ,business ,cardiomyopathy ,Biomarkers - Abstract
With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10−6). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.
- Published
- 2021