Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy

Benjamin Hunter; Yunwei Zhang; Dylan Harney; Holly McEwen; Yen Chin Koay; Michael Pan; Cassandra Malecki; Jasmine Khor; Robert D Hume; Giovanni Guglielmi; Alicia Walker; Shashwati Dutta; Vijay Rajagopal; Anthony Don; Mark Larance; John F O'Sullivan; Jean Y H Yang; Sean Lal

doi:10.1038/s44321-025-00281-9

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Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy

Benjamin Hunter, Yunwei Zhang, Dylan Harney, Holly McEwen, Yen Chin Koay, Michael Pan, Cassandra Malecki, Jasmine Khor, Robert D Hume, Giovanni Guglielmi, …

EMBO molecular medicine

2025

DOI: https://doi.org/10.1038/s44321-025-00281-9

PMID: 40759793

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Abstract

Ischaemic Cardiomyopathy

Confocal Microscopy

Diabetes

Human Myocardium

Multi-omics

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.

Details

Title: Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy
Authors/Creators: Benjamin Hunter - The University of Sydney
Yunwei Zhang - Murdoch University, School of Mathematics, Statistics, Chemistry and Physics
Dylan Harney - The University of Sydney
Holly McEwen - University of Newcastle Australia
Yen Chin Koay - The University of Sydney
Michael Pan - The University of Melbourne
Cassandra Malecki - The University of Sydney
Jasmine Khor - The University of Sydney
Robert D Hume - The University of Sydney
Giovanni Guglielmi - The University of Sydney
Alicia Walker - The University of Sydney
Shashwati Dutta - The University of Sydney
Vijay Rajagopal - The University of Melbourne
Anthony Don - The University of Sydney
Mark Larance - The University of Sydney
John F O'Sullivan - Technische Universität Dresden
Jean Y H Yang - The University of Sydney
Sean Lal - The University of Sydney
Publication Details: EMBO molecular medicine
Publisher: EMBO Press
Grant note: 104853 / National Heart Foundation of Australia (Heart Foundation) 105595 / National Heart Foundation of Australia (Heart Foundation) 2024161 / R.T. Hall Trust (Estate of Late R.T. Hall) G212785 / Federal Government | DHAC | National Health and Medical Research Council (NHMRC) RQ112 / R.T. Hall Trust (Estate of Late R.T. Hall)
Identifiers: 991005800848707891
Murdoch Affiliation: School of Mathematics, Statistics, Chemistry and Physics
Language: English
Resource Type: Journal article

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