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

Author

Listed:
  • Mengbo Li

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Benjamin L. Parker

    (The University of Sydney
    The University of Melbourne)

  • Evangeline Pearson

    (The University of Sydney
    The University of Sydney)

  • Benjamin Hunter

    (The University of Sydney
    The University of Sydney)

  • Jacob Cao

    (The University of Sydney
    The University of Sydney)

  • Yen Chin Koay

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Oneka Guneratne

    (The University of Sydney
    The University of Sydney)

  • David E. James

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Jean Yang

    (The University of Sydney
    The University of Sydney)

  • Sean Lal

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    Royal Prince Alfred Hospital)

  • John F. O’Sullivan

    (The University of Sydney
    The University of Sydney
    The University of Sydney
    The University of Sydney)

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.

Suggested Citation

  • Mengbo Li & Benjamin L. Parker & Evangeline Pearson & Benjamin Hunter & Jacob Cao & Yen Chin Koay & Oneka Guneratne & David E. James & Jean Yang & Sean Lal & John F. O’Sullivan, 2020. "Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16584-z
    DOI: 10.1038/s41467-020-16584-z
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