Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies
Abstract The left and right ventricles of the human heart are functionally and developmentally distinct such that genetic or acquired insults can cause dysfunction in one or both ventricles resulting in heart failure. To better understand ventricle-specific molecular changes influencing heart failur...
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07306-y |
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| author | Benjamin Hunter Mengbo Li Benjamin L. Parker Yen Chin Koay Dylan J. Harney Evangeline Pearson Jacob Cao Gavin T. Chen Oneka Guneratne Gordon K. Smyth Mark Larance John F. O’Sullivan Sean Lal |
| author_facet | Benjamin Hunter Mengbo Li Benjamin L. Parker Yen Chin Koay Dylan J. Harney Evangeline Pearson Jacob Cao Gavin T. Chen Oneka Guneratne Gordon K. Smyth Mark Larance John F. O’Sullivan Sean Lal |
| author_sort | Benjamin Hunter |
| collection | DOAJ |
| description | Abstract The left and right ventricles of the human heart are functionally and developmentally distinct such that genetic or acquired insults can cause dysfunction in one or both ventricles resulting in heart failure. To better understand ventricle-specific molecular changes influencing heart failure development, we first performed unbiased quantitative mass spectrometry on pre-mortem non-diseased human myocardium to compare the metabolome and proteome between the normal left and right ventricles. Constituents of gluconeogenesis, glycolysis, lipogenesis, lipolysis, fatty acid catabolism, the citrate cycle and oxidative phosphorylation were down-regulated in the left ventricle, while glycogenesis, pyruvate and ketone metabolism were up-regulated. Inter-ventricular significance of these metabolic pathways was then found to be diminished within end-stage dilated cardiomyopathy and ischaemic cardiomyopathy, while heart failure-associated pathways were increased in the left ventricle relative to the right within ischaemic cardiomyopathy, such as fluid sheer-stress, increased glutamine-glutamate ratio, and down-regulation of contractile proteins, indicating a left ventricular pathological bias. |
| format | Article |
| id | doaj-art-7209c30a1a994731bc4e81152a7db236 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-7209c30a1a994731bc4e81152a7db2362025-08-20T02:31:55ZengNature PortfolioCommunications Biology2399-36422024-12-017111710.1038/s42003-024-07306-yProteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathiesBenjamin Hunter0Mengbo Li1Benjamin L. Parker2Yen Chin Koay3Dylan J. Harney4Evangeline Pearson5Jacob Cao6Gavin T. Chen7Oneka Guneratne8Gordon K. Smyth9Mark Larance10John F. O’Sullivan11Sean Lal12Precision Cardiovascular Laboratory, The University of SydneyBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, ParkvilleDepartment of Anatomy and Physiology, The University of MelbournePrecision Cardiovascular Laboratory, The University of SydneyCharles Perkins Centre, The University of SydneyPaediatric Oncology and Haematology, Oxford Children’s Hospital, Oxford University Hospitals NHS Foundation TrustCentral Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of SydneyDepartment of Cardiology, Royal Prince Alfred HospitalKolling Institute, Royal North Shore Hospital, and Charles Perkins Centre, Faculty of Medicine and Health, University of SydneyBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, ParkvilleCharles Perkins Centre, The University of SydneyPrecision Cardiovascular Laboratory, The University of SydneyPrecision Cardiovascular Laboratory, The University of SydneyAbstract The left and right ventricles of the human heart are functionally and developmentally distinct such that genetic or acquired insults can cause dysfunction in one or both ventricles resulting in heart failure. To better understand ventricle-specific molecular changes influencing heart failure development, we first performed unbiased quantitative mass spectrometry on pre-mortem non-diseased human myocardium to compare the metabolome and proteome between the normal left and right ventricles. Constituents of gluconeogenesis, glycolysis, lipogenesis, lipolysis, fatty acid catabolism, the citrate cycle and oxidative phosphorylation were down-regulated in the left ventricle, while glycogenesis, pyruvate and ketone metabolism were up-regulated. Inter-ventricular significance of these metabolic pathways was then found to be diminished within end-stage dilated cardiomyopathy and ischaemic cardiomyopathy, while heart failure-associated pathways were increased in the left ventricle relative to the right within ischaemic cardiomyopathy, such as fluid sheer-stress, increased glutamine-glutamate ratio, and down-regulation of contractile proteins, indicating a left ventricular pathological bias.https://doi.org/10.1038/s42003-024-07306-y |
| spellingShingle | Benjamin Hunter Mengbo Li Benjamin L. Parker Yen Chin Koay Dylan J. Harney Evangeline Pearson Jacob Cao Gavin T. Chen Oneka Guneratne Gordon K. Smyth Mark Larance John F. O’Sullivan Sean Lal Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies Communications Biology |
| title | Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies |
| title_full | Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies |
| title_fullStr | Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies |
| title_full_unstemmed | Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies |
| title_short | Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies |
| title_sort | proteomic and metabolomic analyses of the human adult myocardium reveal ventricle specific regulation in end stage cardiomyopathies |
| url | https://doi.org/10.1038/s42003-024-07306-y |
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