Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies
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.
Authors
- John O’Sullivan (ORCID: https://orcid.org/0000-0001-8016-5128)
- Yen Chin Koay (ORCID: https://orcid.org/0000-0002-6704-5495)
- Benjamin Hunter (ORCID: https://orcid.org/0000-0001-6100-9760)
- Mark Larance (ORCID: https://orcid.org/0000-0002-8579-2267)
- Jacob Cao (ORCID: https://orcid.org/0000-0001-6542-8786)
- Mengbo Li (ORCID: https://orcid.org/0000-0002-9666-5810)
- Benjamin L. Parker (ORCID: https://orcid.org/0000-0003-1818-2183)
- Gavin T. Chen (ORCID: https://orcid.org/0000-0002-6041-9749)
- Sean Lal (ORCID: https://orcid.org/0000-0002-5841-560X)
- Gordon K. Smyth (ORCID: https://orcid.org/0000-0001-9221-2892)
- Evangeline Pearson
- Dylan Harney (ORCID: https://orcid.org/0000-0002-1148-5838)
- Oneka Guneratne
Institutions
- The University of Sydney (AU)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Royal Prince Alfred Hospital (AU)
- Royal North Shore Hospital (AU)
- The Heart Research Institute (AU)
- Oxford University Hospitals NHS Trust (GB)
- Baird Institute (AU)
- Technische Universität Dresden (DE)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-12-19
- DOI
- https://doi.org/10.1038/s42003-024-07306-y
- Citations
- 2
- Primary Topic
- Cardiovascular Function and Risk Factors
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- National Heart Foundation of Australia
- R.T. Hall Trust
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council