ORIGINAL RESEARCH article
Front. Physiol.
Sec. Metabolic Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1638179
Tissue Metabolomics Reveals Metabolic Dysregulation Associated with Intimal Hyperplasia in Arteriovenous Fistula Stenosis
Provisionally accepted
- 13201 Hospital, Hanzhong, China
- 2Shaanxi University of Technology, Hanzhong, China
- 3Nanchang University, Nanchang, China
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This study performed untargeted LC-MS metabolomics on venous tissues from maintenance hemodialysis patients undergoing arteriovenous fistula (AVF) reconstruction surgery. (A total of six stenotic and six non-stenotic AVF tissues were analyzed.)Paired samples were collected from stenotic AVF segments and non-stenotic regions (control group). Histological analysis revealed significant intimal hyperplasia in stenotic tissues (687.90±149.00 μm vs 286.70±95.18 μm , P<0.0001 by HE staining) and excessive collagen deposition (Masson staining). Metabolomic profiling identified 802 metabolites, with 356 differentially expressed (VIP>1, P<0.05), predominantly lipids/lipid-like molecules. KEGG enrichment highlighted five dysregulated pathways (P<0.01): 1) Arginine/proline metabolism 2) Glycerophospholipid metabolism 3) ABC transporters 4) Choline metabolism in cancer 5) Retrograde endocannabinoid signaling Six metabolites showed perfect diagnostic potential (AUC=1.0): niacin, free carnitine, 3-hydroxynonyl-5,7-dienoylcarnitine, 3-methylheptanediylcarnitine, dec-7-enoylcarnitine, and γ-aminobutyric acid. Significant metabolite-clinical correlations included: • Choline positively correlating with serum phosphorus (r=0.62, P=0.008) • Carnitine associating with hemoglobin levels (r=0.58,P=0.012) This tissue-based metabolomics study defines specific metabolic disturbances driving AVF stenosis, proposing mechanistic insights and candidate biomarkers.
Keywords: Metabolomics, end-stage renal disease, arteriovenous fistula stenosis, biomarkers, Intimal hyperplasia
Received: 30 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Zhao, Wu, Zhao, Nian, Li and Lu. 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:
Wanjun Li, 3201 Hospital, Hanzhong, China
Hongzhao Lu, Shaanxi University of Technology, Hanzhong, China
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