ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Metabolomics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1673430
Untargeted Metabolomics Unveils Metabolic Biomarkers in HFpEF
Provisionally accepted
- First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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Background: Heart failure with preserved ejection fraction (HFpEF) is a complex condition linked to metabolic disturbances. This study aimed to identify plasma metabolic signatures in HFpEF patients using untargeted metabolomic profiling. Methods: We analyzed data from 30 HFpEF patients and 30 matched healthy controls. Untargeted metabolomic profiling via UHPLC-MS/MS was conducted on venous blood to identify metabolic differences. Initial analyses included principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and hierarchical clustering to detect differing compound groups. Receiver operating characteristic (ROC) curve analysis and pathway enrichment were performed to identify dysregulated genes. Finally, enzyme-linked immunosorbent assay (ELlSA) was used to validate the serum levels of selected metabolites. Results: A total of 124 significantly different metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.833, P < 0.05). Lipids and lipid-like molecules were notably altered in HFpEF patients. KEGG enrichment analysis indicated these metabolites were primarily involved in tryptophan metabolism. Hierarchical clustering showed distinct compound levels between groups. ROC curve analysis revealed PC 18:1-20:5 (AUC: 0.833) and PC 18:1-18:1 (AUC: 0.824) as key metabolites. ELlSA validation confirmed that serum Kynurenine and IAA levels were significantly elevated in HFpEF patients compared to HCs (p<0.05).
Keywords: HFPEF, Metabolomics, tryptophan metabolism, indole, Kynurenine, biomarker
Received: 25 Jul 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 Mahemuti, Duan, Abudurexiti, Abuduhalike and Aimaier. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ailiman Mahemuti, 1453421013@stu.xjmu.edu.cn
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