Heart failure (HF) is a major clinical concern owing to its high prevalence and high mortality. Metabolomics, an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis, has been extensively applied in evaluating the course of diseases. In this study, we used this approach to analyse the abundance of metabolites, with liquid chromatograph-mass spectrometer, in plasma samples from rats with transverse aortic constriction (TAC) and patients at different stages of HF. We compared the metabolic parameters within and between TAC rats and patients. An apparent metabolic shift was observed in rats, from compensated hypertrophy stage to decompensated hypertrophy stage, and in patients with HF, from stage A to stage B and subsequently stage C. Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients. Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways, and those interfered at different stages and across species were confirmed. The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis, hinted at novel potential biomarkers, and provided potential therapeutic intervention targets for HF.
Keywords: HF stages A–C; TAC; biomarker; heart failure; metabolomics; pathway analysis.