Identification of Neointimal Hyperplasia-Associated Extracellular Matrix Proteins in Arteriovenous Graft Fistula Using Bioinformatics and Analysis of Molecular Mechanisms

doi:10.3870/j.issn.1672-8009.2026.05.011

Abstract

Abstract: Objective To screen extracellular matrix （ECM） proteins associated with neointimal hyperplasia （NH） in arteriovenous graft （AVG） fistula using bioinformatics methods, explore the underlying molecular mechanisms, and provide novel molecular targets and drug candidates for clinical treatment. Methods The dataset GSE97377 was obtained from the GEO database. Transcriptomic data on day 14 after AVG modeling served as the training set, and data on day 5 served as the validation set. Differentially expressed genes （DEGs） were identified using the limma package. ECM proteins were extracted from the Uniprot and HPA databases, and intersection with DEGs was performed to obtain ECM protein-related DEGs （EP-DEGs）. GO and KEGG pathway analyses were conducted on EP-DEGs. A protein-protein interaction network was constructed to screen for hub genes. Functional analysis of EP-DEGs was performed using the GeneMANIA database. Drug prediction and molecular docking were carried out using the DSigDB and CB-DOCK2 databases, respectively. Results A total of 79 EP-DEGs associated with NH development after AVG fistula were identified, among which IL1A, CXCL12, CD163, and SPP1 were identified as key hub genes. GO and KEGG analyses indicated that these genes were primarily involved in inflammatory response and ECM remodeling. The expression levels of CXCL12, CD163, and SPP1 were consistent in the venous vasculature on both day 5 and day 14 after AVG modeling. GeneMANIA analysis suggested that CXCL12 is a key regulator of inflammatory factors. Drug prediction analysis revealed that simvastatin, felodipine, kaempferol, and vorinostat may exert therapeutic effects by targeting the hub genes. Molecular docking analysis demonstrated strong interactions between the target proteins and candidate drugs. Conclusion This study systematically identified ECM proteins associated with NH after AVG fistula and predicted multiple potential molecular targets and candidate drugs, providing a theoretical basis for understanding the molecular mechanisms of NH and developing novel therapeutic strategies.

Key words: maintenance hemodialysis, arteriovenous hemodialysis graft, neointimal hyperplasia, extracellular matrix proteins, molecular docking

CLC Number:

R654.3

JIANG Lihua, JIN Ailian, LONG Yanhong, BIE Zirui. Identification of Neointimal Hyperplasia-Associated Extracellular Matrix Proteins in Arteriovenous Graft Fistula Using Bioinformatics and Analysis of Molecular Mechanisms[J]. Journal of Medical Molecular Biology, 2026, 23(5): 563-570.

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