Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies

Hunter, B; Li, M; Parker, BL; Koay, YC; Harney, DJ; Pearson, E; Cao, J; Chen, GT; Guneratne, O; Smyth, GK; Larance, M; O&#39;Sullivan, JF; Lal, S

Author(s): Hunter, B; Li, M; Parker, BL; Koay, YC; Harney, DJ; Pearson, E; Cao, J; Chen, GT; Guneratne, O; Smyth, GK; Larance, M; O'Sullivan, JF; Lal, S;
Details: Publication Year 2024-12-19,Volume 7,Issue #1,Page 1666
Journal Title: Communications Biology
Abstract: 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.
Publisher: Springer Nature
Keywords: Humans; *Heart Ventricles/metabolism; *Proteomics/methods; *Cardiomyopathies/metabolism; *Myocardium/metabolism; *Metabolomics/methods; Male; Middle Aged; Female; Adult; Aged; Metabolome; Proteome/metabolism
Research Division(s): Bioinformatics
PubMed ID: 39702518
Publisher's Version: https://doi.org/10.1038/s42003-024-07306-y
Open Access at Publisher's Site: https://doi.org/0.1038/s42003-024-07306-y
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-01-20 03:39:09

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