Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy
Ischaemic cardiomyopathy is the most common cause of heart failure and often coexists with diabetes mellitus, which worsens patient symptom burden and outcomes. Yet, their combined effects are seldom investigated and are poorly understood. To uncover the influencing molecular signature defining ischaemic cardiomyopathy with diabetes, we performed multi-omic analyses of ischaemic and non-ischaemic cardiomyopathy with and without diabetes against healthy age-matched donors. Tissue was sourced from pre-mortem human left ventricular myocardium. Fatty acid transport and oxidation proteins were most downregulated in ischaemic cardiomyopathy with diabetes relative to donors. However, the downregulation of acylcarnitines, perilipin, and ketone body, amino acid, and glucose metabolising proteins indicated lipid metabolism may not be entirely impaired. Oxidative phosphorylation, oxidative stress, myofibrosis, and cardiomyocyte cytoarchitecture also appeared exacerbated principally in ischaemic cardiomyopathy with diabetes. These findings indicate that diabetes confounds the pathological phenotype in heart failure, and the need for a paradigm shift regarding lipid metabolism.
Authors
- John O’Sullivan (ORCID: https://orcid.org/0000-0001-8016-5128)
- Yen Chin Koay (ORCID: https://orcid.org/0000-0002-6704-5495)
- Cassandra Malecki (ORCID: https://orcid.org/0000-0002-2367-9541)
- Benjamin Hunter (ORCID: https://orcid.org/0000-0001-6100-9760)
- Mark Larance (ORCID: https://orcid.org/0000-0002-8579-2267)
- Shashwati Dutta
- Jean Yang (ORCID: https://orcid.org/0000-0002-5271-2603)
- Jasmine Khor (ORCID: https://orcid.org/0000-0002-3214-2412)
- Anthony S. Don (ORCID: https://orcid.org/0000-0003-1655-1184)
- Sean Lal (ORCID: https://orcid.org/0000-0002-5841-560X)
- Vijay Rajagopal (ORCID: https://orcid.org/0000-0002-5509-402X)
- Michael Pan (ORCID: https://orcid.org/0000-0002-8978-7350)
- Holly P. McEwen (ORCID: https://orcid.org/0000-0002-8233-1553)
- Dylan Harney (ORCID: https://orcid.org/0000-0002-1148-5838)
- Robert D. Hume (ORCID: https://orcid.org/0000-0003-3694-9333)
- Yunwei Zhang (ORCID: https://orcid.org/0000-0003-2173-3185)
- Giovanni Guglielmi (ORCID: https://orcid.org/0000-0001-8253-2446)
- A. J. Walker
Institutions
- The University of Sydney (AU)
- The University of Melbourne (AU)
- Royal Prince Alfred Hospital (AU)
- The Heart Research Institute (AU)
- Australian Mathematical Sciences Institute (AU)
- Melbourne Health (AU)
- Baird Institute (AU)
- Technische Universität Dresden (DE)
- University of Newcastle Australia (AU)
- University of Birmingham (GB)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1038/s44321-025-00281-9
- Citations
- 4
- Primary Topic
- Cardiovascular Function and Risk Factors
- Type
- article
- Field-Weighted Citation Impact
- 5.55
Funders
- National Heart Foundation of Australia
- R.T. Hall Trust
- National Health and Medical Research Council