Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy

Mengbo Li, Benjamin L. Parker, Evangeline Pearson, Benjamin Hunter, Jacob Cao, Yen Chin Koay, Oneka Guneratne, David E. James, Jean Yang, Sean Lal () and John F. O’Sullivan ()
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Mengbo Li: The University of Sydney
Benjamin L. Parker: The University of Sydney
Evangeline Pearson: The University of Sydney
Benjamin Hunter: The University of Sydney
Jacob Cao: The University of Sydney
Yen Chin Koay: The University of Sydney
Oneka Guneratne: The University of Sydney
David E. James: The University of Sydney
Jean Yang: The University of Sydney
Sean Lal: The University of Sydney
John F. O’Sullivan: The University of Sydney

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Poor access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a carefully procured large human heart biobank of cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide. We perform unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, compared to age-, gender-, and BMI-matched, histopathologically normal, donor controls. We report a dramatic reduction in serum amyloid A1 protein in ICM hearts, perturbed thyroid hormone signalling pathways and significant reductions in oxidoreductase co-factor riboflavin-5-monophosphate and glycolytic intermediate fructose-6-phosphate in both; unveil gender-specific changes in HF, including nitric oxide-related arginine metabolism, mitochondrial substrates, and X chromosome-linked protein and metabolite changes; and provide an interactive online application as a publicly-available resource.

Date: 2020
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DOI: 10.1038/s41467-020-16584-z

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