Ventricle-specific myocardial protein and metabolite characterisation in healthy humans, with differential regulation in end-stage cardiomyopathies

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. First, we performed unbiased quantitative mass spectrometry on the myocardium of 25-27 pre-mortem cryopreserved non-diseased human hearts 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 (n = 30-33), 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 to glutamate ratio, and down-regulation of contractile proteins indicating a left ventricular pathological bias.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

SUBMITTER: Mark Larance  

LAB HEAD: Mark Larance

PROVIDER: PXD042155 | Pride | 2024-11-06

REPOSITORIES: Pride