{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Flam E"],"funding":["Edward Mallinckrodt, Jr. Foundation","NIA NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS","U.S. Department of Defense","George Gund Foundation","Blavatnik Family Foundation","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","NIGMS NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["817-829"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9910091"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["1(9)"],"pubmed_abstract":["Heart failure (HF) is a leading cause of mortality. Failing hearts undergo profound metabolic changes, but a comprehensive evaluation in humans is lacking. We integrate plasma and cardiac tissue metabolomics of 678 metabolites, genome-wide RNA-sequencing, and proteomic studies to examine metabolic status in 87 explanted human hearts from 39 patients with end-stage HF compared with 48 nonfailing donors. We confirm bioenergetic defects in human HF and reveal selective depletion of adenylate purines required for maintaining ATP levels. We observe substantial reductions in fatty acids and acylcarnitines in failing tissue, despite plasma elevations, suggesting defective import of fatty acids into cardiomyocytes. Glucose levels, in contrast, are elevated. Pyruvate dehydrogenase, which gates carbohydrate oxidation, is de-repressed, allowing increased lactate and pyruvate burning. Tricarboxylic acid cycle intermediates are significantly reduced. Finally, bioactive lipids are profoundly reprogrammed, with marked reductions in ceramides and elevations in lysoglycerophospholipids. These data unveil profound metabolic abnormalities in human failing hearts."],"journal":["Nature cardiovascular research"],"pubmed_title":["Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy."],"pmcid":["PMC9910091"],"funding_grant_id":["R01 HL105993","HL152446","P30 DK019525","T32 HL007954","HL089847","HL105993","R01 HL152446","R01 GM132261","R01 AG017022","W81XWH18-1-0503","AG17022","R01 HL089847","HL 7954-20","F30 HL142186","GM132261","HL142186","DK019525"],"pubmed_authors":["Rabinowitz JD","Jang C","Morley MP","Flam E","Pepper H","Prosser BL","Margulies KB","Kantner DS","Yang Y","Bedi KC","Cappola T","Brandimarto J","Murashige D","Jung S","Snyder NW","Arany Z"],"additional_accession":[]},"is_claimable":false,"name":"Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy.","description":"Heart failure (HF) is a leading cause of mortality. Failing hearts undergo profound metabolic changes, but a comprehensive evaluation in humans is lacking. We integrate plasma and cardiac tissue metabolomics of 678 metabolites, genome-wide RNA-sequencing, and proteomic studies to examine metabolic status in 87 explanted human hearts from 39 patients with end-stage HF compared with 48 nonfailing donors. We confirm bioenergetic defects in human HF and reveal selective depletion of adenylate purines required for maintaining ATP levels. We observe substantial reductions in fatty acids and acylcarnitines in failing tissue, despite plasma elevations, suggesting defective import of fatty acids into cardiomyocytes. Glucose levels, in contrast, are elevated. Pyruvate dehydrogenase, which gates carbohydrate oxidation, is de-repressed, allowing increased lactate and pyruvate burning. Tricarboxylic acid cycle intermediates are significantly reduced. Finally, bioactive lipids are profoundly reprogrammed, with marked reductions in ceramides and elevations in lysoglycerophospholipids. These data unveil profound metabolic abnormalities in human failing hearts.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-03-18T14:07:06.155Z","creation":"2025-04-04T20:03:45.594Z"},"accession":"S-EPMC9910091","cross_references":{"pubmed":["36776621"],"doi":["10.1038/s44161-022-00117-6"]}}