ArticlePloS one2014
The role of Iex-1 in the pathogenesis of venous neointimal hyperplasia associated with hemodialysis arteriovenous fistula.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- The Multi-Dimensional Role of Vitamin D in the Pathophysiology and Treatment of Diabetic Foot Ulcers: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Review
- Functions for platelet factor 4 (PF4/CXCL4) and its receptors in fibroblast-myofibroblast transition and fibrotic failure of arteriovenous fistulas (AVFs).The journal of vascular access · 2024Article
- Review
- Regulation of vascular remodeling by immune microenvironment after the establishment of autologous arteriovenous fistula in ESRD patients.Frontiers in immunology · 2024Review
- Integrating transcriptomics, eQTL, and Mendelian randomization to dissect monocyte roles in severe COVID-19 and gout flare.Frontiers in genetics · 2024Article
- Comprehensive analysis of hypoxia-related genes in diagnosis and immune infiltration in acute myocardial infarction: based on bulk and single-cell RNA sequencing data.Frontiers in molecular biosciences · 2024Article
- Sex hormones impact early maturation and immune response in the arteriovenous fistula mouse model.American journal of physiology. Heart and circulatory physiology · 2023Article
- Sex Differences in Arteriovenous Fistula Failure: Insights from Bioinformatics Analysis.Journal of cardiovascular development and disease · 2022Article
- Bindarit encapsulated nanoparticles prevent venous neointimal hyperplasia and restenosis in a murine angioplasty model.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use.Biomolecules · 2022Review
- Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse Model.Journal of the American Society of Nephrology : JASN · 2021Article
- Adventitial delivery of nanoparticles encapsulated with 1α, 25-dihydroxyvitamin DScientific reports · 2021Article
- Periadventitial Delivery of Simvastatin-Loaded Microparticles Attenuate Venous Neointimal Hyperplasia Associated With Arteriovenous Fistula.Journal of the American Heart Association · 2020Article
- Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model.Journal of the American Society of Nephrology : JASN · 2020Article
- Effect of sex differences in treatment response to angioplasty in a murine arteriovenous fistula model.American journal of physiology. Renal physiology · 2020Article
- Evaluation of Venous Stenosis Angioplasty in a Murine Arteriovenous Fistula Model.Journal of vascular and interventional radiology : JVIR · 2019Article
- Increased transforming growth factor beta (TGF-β) and pSMAD3 signaling in a Murine Model for Contrast Induced Kidney Injury.Scientific reports · 2018Article
- Significance of blood and salivary IEX-1 expression in diagnosis of epithelial ovarian carcinoma.The journal of obstetrics and gynaecology research · 2018Article
- Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells.Cardiovascular research · 2017Article
- CorMatrix Wrapped Around the Adventitia of the Arteriovenous Fistula Outflow Vein Attenuates Venous Neointimal Hyperplasia.Scientific reports · 2017Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Arteriovenous fistulas (AVFs) used for hemodialysis fail because of venous neointimal hyperplasia (VNH). There are 1,500,000 patients that have end stage renal disease worldwide and the majority requires hemodialysis. In the present study, the role of the intermediate early response gene X-1 (IEX-1), also known as IER-3 in the pathogenesis of VNH was evaluated. In human samples removed from failed AVF, there was a significant increase in IEX-1 expression localized to the adventitia. In Iex-1-/- mice and wild type (WT) controls, chronic kidney disease was induced and an AVF placed 28 days later by connecting the carotid artery to jugular vein. The outflow vein was removed three days following the creation of the AVF and gene expression analysis demonstrated a significant decrease in vascular endothelial growth factor-A (Vegf-A) and monocyte chemoattractant protein-1 (Mcp-1) gene expression in Iex-1-/- mice when compared to WT mice (P<0.05). At 28 days after AVF placement, histomorphometric and immune-histochemical analyses of the outflow vein demonstrated a significant decrease in neointimal hyperplasia with an increase in average lumen vessel area associated with a decrease in fibroblast, myofibroblast, and Ly6C staining. There was a decrease in proliferation (Ki-67) and an increase in the TUNEL staining in Iex-1 KO mice compared to WT. In addition, there was a decrease in Vegf-A, Mcp-1, and matrix metalloproteiniase-9 (Mmp-9) staining. Iex-1 expression was reduced in vivo and in vitro using nanoparticles coated with calcitriol, an inhibitor of Iex-1 that demonstrated that Iex-1 reduction results in decrease in Vegf-A. In aggregate, these results indicate that the absence of IEX-1 gene results in reduced VNH accompanied with a decrease in proliferation, reduced fibroblast, myofibroblast, and Ly6C staining accompanied with increased apoptosis mediated through a reduction in Vegf-A/Mcp-1 axis and Mmp-9. Adventitial delivery of nanoparticles coated with calcitriol reduced Iex-1 and VNH.
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