Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation

Sharma, Gaurav; Kuppler, Christopher; He, Yangang; Tao, Ming; Ding, Kang; Longchamp, Alban; Dember, Laura M.; Ozaki, C. Keith; Berceli, Scott A.

doi:10.1016/j.ekir.2018.02.008

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…18 However, other studies hold the opposite conclusion. They found that IL6 in the adipose tissue around the fistula vein were associated with a reduction in the fractional vein diameter during the early time frame of 1 day to 2 weeks, 37 which shows that IL6 appears to have an early negative effect after AVF creation. In conclusion, the effect of IL6 on AVF maturation has been demonstrated, which is consistent with our experimental results.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Genes and Immune Cell Infiltration Characterize the Maturation Status of Arteriovenous Fistulas: An Integrative Bioinformatics Study and Experimental Validation Based on Transcriptome Sequencing

Lu,

Wang,

Wan

et al. 2024

JIR

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Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, but the low maturation rate is concerning. Immune cells' impact on AVF maturation lacks bioinformatics research. The study aims to investigate the potential predictive role of immune-related genes and immune cell infiltration characteristics in AVF maturation. Patients and Methods: We analyzed the high-throughput sequencing dataset to identify differentially expressed genes (DEGs). Then, we performed enrichment analyses (GO, KEGG, GSEA) on immune-related genes and pathways in mature AVF. We focused on differentially expressed immune-related genes (DEIRGs) and constructed a PPI network to identify hub genes. These hub genes were validated in other databases and experiments, including qPCR and immunohistochemistry (IHC). The immune cell infiltration characteristics in native veins, failed AVFs, and matured AVFs were analyzed by cibersortX. Partial experimental validation was conducted using clinical samples. Results: Our results showed that immune-related genes and signaling pathways are significantly enriched in mature AVF. We validated this in other databases and ultimately identified three hub genes (IL1B, IL6, CXCR4) in combination with experiments. Significant differences in immune cell infiltration characteristics were observed among native veins, failed AVFs, and matured AVFs. Immune cell infiltration analysis revealed that accumulation of CD4+ T cells, dendritic cells, mast cells and M2 macrophages contribute to AVF maturation. These immune-related genes and immune cells have the potential to serve as predictive factors for AVF maturation. We partially validated this experimentally. Conclusion: From a bioinformatics perspective, our results have identified, for the first time, a set of immune-related genes and immune cell infiltration features that can characterize the maturation of AVF and significantly impact AVF maturation. These features hold potential as predictive indicators for AVF maturation outcomes.

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Section: Discussionmentioning

confidence: 99%

Immune-Related Genes and Immune Cell Infiltration Characterize the Maturation Status of Arteriovenous Fistulas: An Integrative Bioinformatics Study and Experimental Validation Based on Transcriptome Sequencing

Lu,

Wang,

Wan

et al. 2024

JIR

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“…The sources and triggers of these circulating factors are not clear at the moment because many of them are ubiquitously produced by hematopoietic and nonhematopoietic cells (58,59,70,76,(84)(85)(86). Immune cell phenotyping studies are needed to assess activation of leukocyte populations and the balance of inflammatory and regulatory cells.…”

Section: Discussionmentioning

confidence: 99%

Systemic Profile of Cytokines in Arteriovenous Fistula Patients and Their Associations with Maturation Failure

et al. 2022

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Background: Systemic cytokines are elevated in chronic kidney disease (CKD) and hemodialysis patients compared to the general population. However, whether cytokine levels interfere with vascular remodeling increasing the risk of arteriovenous fistula (AVF) failure remains unknown. Methods: This is a case-control study of 64 patients who underwent surgery for AVF creation (32 with AVF maturation failure and 32 matching controls with successful maturation). A total of 74 cytokines, including chemokines, interferons, interleukins, and growth factors, were measured in preoperative plasma samples using multiplex assays. Sixty-two patients were included in the statistical analyses. Associations with AVF failure were assessed using paired comparisons and conditional logistic regressions accounting for paired strata. Results: Seven cytokines were significantly higher in patients with AVF maturation failure than in matching controls (G-CSF, IL-6, MDC, RANTES, SDF-1α/β, TGFα, and TPO). Of these, G-CSF (odds ratio 1.71 [1.05-2.79] per 10 pg/mL), MDC (1.60 [1.08-2.38] per 100 pg/mL), RANTES (1.55 [1.10-2.17] per 100 pg/mL), SDF-1α/β (1.18 [1.04-1.33] per 1000 pg/mL), and TGFα (OR 1.39 [1.003-1.92] per 1 pg/mL) showed an incremental association by logistic regression. Conclusions: This study identified a profile of plasma cytokines associated with adverse maturation outcomes in AVFs. These findings may open the doors for future therapeutics and markers for risk stratification.

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“…Proinflammatory cytokine, such as monocyte chemotactic protein-1 (MCP-1), TNF-α, and interleukin 6 (IL-6), levels are also elevated in the AV fistula venous segment [ 22 , 48 ], which is positively associated with MMP-9 expression in vascular smooth muscle cells [ 49 , 50 , 51 ]. In addition, perivenous adipose MCP-1 and IL-6 levels are inversely related to early postoperative AV fistula veinous segment diameter changes [ 52 ]. MCP-1 knockout reduces AV fistula venous thickness and improves fistula patency, while TNF-α induces neointima after arterial injury via the TNF-α/MMP-9 axis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

MMP-9 Deletion Attenuates Arteriovenous Fistula Neointima through Reduced Perioperative Vascular Inflammation

Shih

Chen

et al. 2021

IJMS

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Matrix metalloproteinase 9 (MMP-9) expression is upregulated in vascular inflammation and participates in vascular remodeling, including aneurysm dilatation and arterial neointima development. Neointima at the arteriovenous (AV) fistula anastomosis site primarily causes AV fistula stenosis and failure; however, the effects of MMP-9 on perioperative AV fistula remodeling remain unknown. Therefore, we created AV fistulas (end-to-side anastomosis) in wild-type (WT) and MMP-9 knockout mice with chronic kidney disease to further clarify this. Neointima progressively developed in the AV fistula venous segment of WT mice during the four-week postoperative course, and MMP-9 knockout increased the lumen area and attenuated neointima size by reducing smooth muscle cell and collagen components. Early perioperative AV fistula mRNA sequencing data revealed that inflammation-related gene sets were negatively enriched in AV fistula of MMP-9 knockout mice compared to that in WT mice. qPCR results also showed that inflammatory genes, including tumor necrosis factor-a (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), were downregulated. In addition, Western blot results showed that MMP-9 knockout reduced CD44 and RAC-alpha serine/threonine-protein kinase (Akt) and extracellular signal-regulated kinases (ERK) phosphorylation. In vitro, MMP-9 addition enhanced IL-6 and MCP-1 expression in vascular smooth muscle cells, as well as cell migration, which was reversed by an MMP-9 inhibitor. In conclusion, MMP-9 knockout attenuated AV fistula stenosis by reducing perioperative vascular inflammation.

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Local Adipose-Associated Mediators and Adaptations Following Arteriovenous Fistula Creation

Cited by 5 publications

References 49 publications

Immune-Related Genes and Immune Cell Infiltration Characterize the Maturation Status of Arteriovenous Fistulas: An Integrative Bioinformatics Study and Experimental Validation Based on Transcriptome Sequencing

Immune-Related Genes and Immune Cell Infiltration Characterize the Maturation Status of Arteriovenous Fistulas: An Integrative Bioinformatics Study and Experimental Validation Based on Transcriptome Sequencing

Systemic Profile of Cytokines in Arteriovenous Fistula Patients and Their Associations with Maturation Failure

MMP-9 Deletion Attenuates Arteriovenous Fistula Neointima through Reduced Perioperative Vascular Inflammation

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