Dataset Information

Gene expression changes in venous segment of overflow arteriovenous fistula.

ABSTRACT: Aim. The objective of this study was to characterize coordinated molecular changes in the structure and composition of the walls of venous segments of arteriovenous (AV) fistulas evoked by overflow. Methods. Venous tissue samples were collected from 6 hemodialysis patients with AV fistulas exposed to overflow and from the normal cephalic veins of 4 other hemodialysis patients. Total RNA was extracted from the venous tissue samples, and gene expression between the 2 groups was compared using Whole Human Genome DNA microarray 44?K. Microarray data were analyzed by GeneSpring GX software and Ingenuity Pathway Analysis. Results. The cDNA microarray analysis identified 397 upregulated genes and 456 downregulated genes. Gene ontology analysis with GeneSpring GX software revealed that biological developmental processes and glycosaminoglycan binding were the most upregulated. In addition, most upregulation occurred extracellularly. In the pathway analysis, the TGF beta signaling pathway, cytokines and inflammatory response pathway, hypertrophy model, and the myometrial relaxation and contraction pathway were significantly upregulated compared with the control cephalic vein. Conclusion. Combining microarray results and pathway information available via the Internet provided biological insight into the structure and composition of the venous wall of overflow AV fistulas.

SUBMITTER: Hashimoto Y

PROVIDER: S-EPMC3655589 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Gene expression changes in venous segment of overflow arteriovenous fistula.

Hashimoto Yasuhiro Y Okamoto Akiko A Saitoh Hisao H Hatakeyama Shingo S Yoneyama Takahiro T Koie Takuya T Ohyama Chikara C

International journal of nephrology 20130427

Aim. The objective of this study was to characterize coordinated molecular changes in the structure and composition of the walls of venous segments of arteriovenous (AV) fistulas evoked by overflow. Methods. Venous tissue samples were collected from 6 hemodialysis patients with AV fistulas exposed to overflow and from the normal cephalic veins of 4 other hemodialysis patients. Total RNA was extracted from the venous tissue samples, and gene expression between the 2 groups was compared using Whol ...[more]

PMID: 23710358

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Project description:Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis. Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein-protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions. Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1. Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.

Project description:Background: Although clinical outcome of arteriovenous fistula (AVF) as a preferred vascular access for hemodialysis has been inadequate, biological mechanisms of AVF maturation and failure is still poorly understood. Since our mouse AVF model recapitulates human AVF maturation and partial failure, we hypothesized that high throughput RNA sequencing (RNA-seq) analysis would identify early changes in gene expression that might predict AVF maturation and failure. Method: Aortocaval fistula creation (AVF group) or sham operation (sham group) was performed with C57BL/6 mice (10 wk). Ultrasound was performed to confirm the AVF patency and to measure hemodynamics. Venous limbs were collected on postoperative day 7 and total RNA was extracted. After Poly-A mRNA libraries were constructed, RNA-seq was performed. Differentially expressed genes (DEG) were identified, and subsequent enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed with bioinformatics techniques. Results: 1057 DEG were identified between the AVF and sham groups. Genes in metabolic pathways were significantly downregulated in the AVF. Since gene expression patterns among the AVF group were significantly heterogenous, the AVF group was divided into 2 groups (‘normal’ AVF group; nAVF and ‘outliers’ group; OUT), and subgroup analyses were performed. Although physiological data of body weight change and hemodynamics were not different between the nAVF and OUT groups, 413 DEG were identified between them. Enrichment analyses showed significant overrepresentation of metabolism, immunity, and coagulation in the OUT group. Comparing the nAVF group with the sham group, 403 DEG were identified. Enrichment analyses showed increase of gene expression related to cell cycle, extracellular matrix, and immunity. Comparing these results with previously published data, the gene expression patterns of the nAVF group was consistent with AVF maturation and adaptive remodeling, whereas the OUT group showed attenuated difference, suggesting the heterogeneity of the AVF group reflects early gene expression changes in the process of AVF maturation and failure. Significant sex differences were not observed in the AVF group. Conclusions: A small subset of AVF undergoes aberrant biological processes in the early phase including diminished ECM remodeling, activated coagulation and upregulated metabolism, that could lead to fistula failure. Detection of these processes might be a viable translational strategy to predict fistula failure and reduce patient morbidity.

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Gene expression changes in venous segment of overflow arteriovenous fistula.

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Gene expression changes in venous segment of overflow arteriovenous fistula.

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