ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1639166
This article is part of the Research TopicUnderstanding Chronic Inflammation: Mechanisms Behind its PersistenceView all 8 articles
Neutrophil Extracellular Traps: A Novel Contributor to Vascular Calcification in Chronic Kidney Disease
Provisionally accepted
- 1Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
- 2The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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Background: Among patients with chronic kidney disease (CKD), vascular calcification significantly contributes to cardiovascular health issues, though the underlying molecular mechanisms remain unclearthough the exact molecular processes are not fully understood. Recent research highlights neutrophil extracellular traps (NETs) as critical mediators of vascular damage and pro-calcific processes. Methods: We obtained transcriptomic data from the NCBI GEO database fromfor CKD mouse rodent models and identified differentially expressed genes, selected genes using machine learninggene selection based on machine learning, functional enrichment, profiling of immune infiltration, transcription factor (TF) activity prediction and drug–gene interaction analysis. Results: Our analysis revealed 36 NET-related genes with differential expression, and 19 were confirmed by the RobustRankAggreg method. Among them, Mmp12 and Comp emerged as the most consistently selected diagnostic markers across five machine learning algorithms, exhibiting excellent predictive performance (AUC > 0.95). These genes were enriched in neutrophil chemotaxis, ECM remodeling, and PI3K-Akt-mTOR signaling pathways. Immunohistochemistry confirmed NET deposition in calcified arteries of rat, and quantitative PCR and Western blot validated key NRGs expression in CKD rat aortae.Elevated NRGs in the aorta of CKD rats were validated using quantitative real-time PCR and Western blot techniques. Conclusion: Our results demonstrate that NET-related genes may contribute to CKD-associated vascular calcification in rodent models. Specifically, this work provides evidence for a potential mechanistic link between NET biology and vascular calcification in CKD, thereby offering insights into immune-vascular interactions and raising the possibility of exploring NET-targeted approaches to mitigate vascular damage.Our results showed a critical role for NET-related genes in CKD associated vascular calcification. This research sheds light on the connection between immunity and vascular systems in CKD, suggesting a foundation for strategies aimed at mitigating vascular damage caused by NETs.
Keywords: CKD, Vascular Calcification, neutrophil extracellular traps, MMP12, comp, machine learning
Received: 01 Jun 2025; Accepted: 08 Sep 2025.
Copyright: © 2025 Wang, Li, Liang and Wan. 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: Jianxin Wan, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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