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Background <p>Autologous arteriovenous fistula is the preferred vascular access for maintenance hemodialysis in patients with end-stage renal disease; however, stenosis remains a common and serious complication that compromises long-term patency. This study aimed to characterize the transcriptomic alterations associated with fistula stenosis and to identify potential biomarkers and therapeutic targets involved in vascular remodeling.</p> Methods <p>Vascular tissue samples were collected as controls from patients during initial arteriovenous fistula construction and as stenotic samples from patients during revision surgery for arteriovenous fistula stenosis, respectively. Histological staining was performed to assess structural changes. High-throughput transcriptome sequencing on an Illumina NovaSeq 6000 platform yielded an average of 76&#xa0;million reads per sample. Differential expression analysis of messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) was conducted using DESeq2 (version 1.42.0), with significance defined as |log₂(Fold Change)| &gt; 1 and an adjusted p-value &lt; 0.05. Functional enrichment analyses of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were performed using the clusterProfiler R package. A protein-protein interaction network was constructed with the STRING database (combined score ≥ 0.900) and visualized in Cytoscape to identify hub genes. A competing endogenous RNA network was assembled to predict lncRNA-miRNA-mRNA interactions. Key inflammatory markers (IL-1β, MCP-1, VCAM-1) were validated by immunohistochemistry.</p> Results <p>Histopathological analysis revealed intimal hyperplasia, smooth muscle cell proliferation, collagen fiber accumulation, and inflammatory cell infiltration in stenotic veins. A total of 1,447 differentially expressed protein-coding genes (1,046 upregulated and 401 downregulated) and 240 long non-coding RNAs (100 upregulated and 140 downregulated) were identified. Enrichment analysis demonstrated significant involvement of immune-inflammatory pathways, cellular adhesion and migration, metabolic dysregulation, and coagulation cascade activation. Protein interaction network analysis suggested that <i>TNF</i>, <i>IL1B</i>, <i>CCL2</i>, <i>VCAM1</i>, <i>CD4</i>, and <i>PTPRC</i> may represent candidate hub genes within the network. A potential regulatory interaction involving <i>LINC01678</i>, hsa-miR-17-5p, and <i>COL8A1</i> was predicted. Immunohistochemistry showed increased expression of interleukin-1β, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 in stenotic tissues.</p> Conclusions <p>By deciphering the molecular landscape of stenotic arteriovenous fistula tissues, this study implicates specific genes and pathways in pathological vascular remodeling. The candidate biomarkers and predicted regulatory networks constitute novel mechanistic hypotheses, warranting further investigation for their therapeutic potential. As these findings are computationally derived, they must be considered preliminary, and experimental validation in larger cohorts is essential to confirm and expand upon these results.</p> Clinical trial number <p>Not applicable.</p>

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Potential biomarkers and regulatory pathways associated with arteriovenous fistula stenosis in end-stage renal disease: an analysis based on transcriptomic profiling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月13日

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  • Ming Zhao,
  • Yuxin An,
  • Wanjun Li,
  • Wei Yang,
  • Wei Chen,
  • Hongzhao Lu

摘要

Background

Autologous arteriovenous fistula is the preferred vascular access for maintenance hemodialysis in patients with end-stage renal disease; however, stenosis remains a common and serious complication that compromises long-term patency. This study aimed to characterize the transcriptomic alterations associated with fistula stenosis and to identify potential biomarkers and therapeutic targets involved in vascular remodeling.

Methods

Vascular tissue samples were collected as controls from patients during initial arteriovenous fistula construction and as stenotic samples from patients during revision surgery for arteriovenous fistula stenosis, respectively. Histological staining was performed to assess structural changes. High-throughput transcriptome sequencing on an Illumina NovaSeq 6000 platform yielded an average of 76 million reads per sample. Differential expression analysis of messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) was conducted using DESeq2 (version 1.42.0), with significance defined as |log₂(Fold Change)| > 1 and an adjusted p-value < 0.05. Functional enrichment analyses of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were performed using the clusterProfiler R package. A protein-protein interaction network was constructed with the STRING database (combined score ≥ 0.900) and visualized in Cytoscape to identify hub genes. A competing endogenous RNA network was assembled to predict lncRNA-miRNA-mRNA interactions. Key inflammatory markers (IL-1β, MCP-1, VCAM-1) were validated by immunohistochemistry.

Results

Histopathological analysis revealed intimal hyperplasia, smooth muscle cell proliferation, collagen fiber accumulation, and inflammatory cell infiltration in stenotic veins. A total of 1,447 differentially expressed protein-coding genes (1,046 upregulated and 401 downregulated) and 240 long non-coding RNAs (100 upregulated and 140 downregulated) were identified. Enrichment analysis demonstrated significant involvement of immune-inflammatory pathways, cellular adhesion and migration, metabolic dysregulation, and coagulation cascade activation. Protein interaction network analysis suggested that TNF, IL1B, CCL2, VCAM1, CD4, and PTPRC may represent candidate hub genes within the network. A potential regulatory interaction involving LINC01678, hsa-miR-17-5p, and COL8A1 was predicted. Immunohistochemistry showed increased expression of interleukin-1β, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 in stenotic tissues.

Conclusions

By deciphering the molecular landscape of stenotic arteriovenous fistula tissues, this study implicates specific genes and pathways in pathological vascular remodeling. The candidate biomarkers and predicted regulatory networks constitute novel mechanistic hypotheses, warranting further investigation for their therapeutic potential. As these findings are computationally derived, they must be considered preliminary, and experimental validation in larger cohorts is essential to confirm and expand upon these results.

Clinical trial number

Not applicable.