| Literature DB >> 33670449 |
Jan Haas1,2, Karen S Frese1,2, Farbod Sedaghat-Hamedani1,2, Elham Kayvanpour1,2, Rewati Tappu1,2, Rouven Nietsch1, Oguz Firat Tugrul1,2, Michael Wisdom1,2, Carsten Dietrich3, Ali Amr1,2, Tanja Weis1,2, Torsten Niederdränk3, Michael P Murphy4, Thomas Krieg5, Marcus Dörr2,6, Uwe Völker2,7, Jens Fielitz2,6, Norbert Frey1,2, Stephan B Felix2,6, Andreas Keller8, Hugo A Katus1,2, Benjamin Meder1,2,9.
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.Entities:
Keywords: cardiomyopathy; energy metabolism; heart failure; multi-omics
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Year: 2021 PMID: 33670449 PMCID: PMC7923201 DOI: 10.3390/ijms22041999
Source DB: PubMed Journal: Int J Mol Sci ISSN: 1422-0067 Impact factor: 5.923